Author: Harneet Marwah ,Tarun Garg, Amit K. Goyal &Goutam Rath

74% of drugs are taken orally and are not found to be as effective as desired, to improve such characteristics, transdermal drug delivery was brought to existence, this delivery system is capable of transporting the drug or macromolecules painlessly through skin into the blood circulation at fixed rate. Topical administration of therapeutic agents offers many advantages over conventional oral and invasive techniques of drug delivery, several important advantages of transdermal drug delivery are prevention from hepatic first pass metabolism, enhancement of therapeutic efficiency and maintenance of steady plasma level of the drug Human skin surface, as a site of drug application for both local and systemic effects, is the most eligible candidate available. New controlled transdermal drug delivery systems (TDDS) technologies (electrically based, structure-based and velocity-based) have been developed and commercialized for the transdermal delivery of troublesome drugs. This review article covers most of the new active transport technologies involved in enhancing the transdermal permeation via effective drug delivery system, Transdermal delivery system can transport the drug through skin into the blood circulation at fixed rate. Transdermal route gives an alternative to oral and i.v. delivery, local delivery is properly documented which includes targeted delivery, lower systemic exposure, and lower toxicity than oral medications. This system is also helpfull in the treatment of hair loss, neuropathic pain, acne, genital herpes, migraine, headaches, and sexual dysfunction, Transdermal delivery avoids the stomach environment where the drug can be degraded , Transdermal delivery avoids the first pass effect where active drug molecules can be converted to inactive molecules or even to molecules responsible for side effects, Provides steady plasma levels, easy to use and non-invasive, drug input can be stopped at any point after removal of the patch from the site , Increases compliance and reduces medical costs, Improves bioavailability, Best route for pediatrics patients, Suitable route for unconsious or vomiting patient, Lesser chances of overdose and easy detection of drug, Human skin: penetration barrier, Stratum corneum, Dermis, Hypodermis, Drug can be penetrated by three pathways such as transcellular route, paracellular lipid route and transappendgeal- route ,Transcellular Route: Moeity passes through both keratinocytes and lipids (straight path to the dermis), Paracellular Route: The most common penetration pathway of drug molecules. In this pathway, drug remains in lipid moeity and stay around keratin (easy for lipid soluble drug rather than proteins) , Transappendgeal Route: It makes continues channel for drug permeation but it hindered easily due to presence of hair follicles and sweat ducts, Physiochemical properties of the drug delivery system, release characteristics, drug release mechanism mainly depends on drug molecules which are dissolved or suspended in the delivery system and on interfacial partition coefficient or pH of the drug from delivery system to the skin tissue. If the drug is easily released from the delivery system, the rate of transdermal permeation will be higher, composition of drug delivery system, Composition may not affect release properties but may affect its permeability functionality. For example, methyl salicylate is more lipophilic than parent acid, and its percutaneous absorption is high when applied to skin in a lipoidal vehicle, Enhancement of transdermal permeation, majority of drugs will not permeate into skin for therapeutic use. Some enhancers are used for synergistic action without showings its properties), Strategies applied for permeation enhancement, drawback of transdermal delivery is permeation of active moeity through skin. So, various studies are done for enhancing its permeability percutaneously. Figure 3 depicts various strategies for increment of penetration. They act by three mechanisms: (1) By altering physicochemical properties of stratum corneum, (2) By changing hydrating property of stratum corneum, (3) By altering structure of lipids and protein in intercellular channel via carrier mechanism, Drug/vehicle interaction, Drug and prodrug selection, Active ingredient to be used should be judiciously chosen on the bases of pharmacological or physiochemical properties, Ideal properties for drug selection are: Less than 600 Da is preferred when diffusion coefficient is high, Good solubility in oil and water, High and adequate partition coefficient (1–3), Should carry melting point minor than 200?F, It should not metabolize in skin, Chemical enhancers help in permeation across the skin by disruption of the highly ordered structure of stratum corenum lipid, interaction with intercellular protein or improve partition of the drug into stratum corneum

Author: Barbara Joanna Ba?an , Marcin Niemcewicz, Janusz Kocik , Leszek Jung , Ewa Skopi?ska-Ró?ewska , Piotr Skopi?ski

aloe gel; antibody production; chemokinesis; mice; proliferation; splenocytes, antimicrobial activity, dietary supplement, Immunomodulation, chronic infections, polysaccharides (pectins, hemicelluloses, glucomannan, acemannan, and other mannose derivatives), stimulatory effect, Aloe vera extract, an increase in CD4 lymphocyte frequency in blood and serum immunoglobulin concentrations

Author: Eli Harlev , Eviatar Nevo , Ephraim P. Lansky , Rivka Ofir , Anupam Bishayee

Aloe vera; acemannan; applications; biological activity; polysaccharide; structure, immunoregulation, anti-cancer, anti-oxidation, wound healing and bone proliferation promotion, neuroprotection, and intestinal health promotion activities, structure-activity relationships of acemannan, medical applications, pharmacological applications of acemannan, neuroprotection, and intestinal health promotion activities, prevention or treatment of skin diseases, metabolic diseases, cardiovascular diseases and cancers, immunomodulation, antimicrobial, antiviral, anti?cancer, anti?inflammatory properties, Polysaccharide acetylation, Acemannan, a ??(1,4)?acetylated soluble polymannose, immunomodulatory activity of acemannan on splenic lymphocyte, macrophage and dendritic cell, adaptive immune system and the innate immune system

Authors Eli Harlev1,Eviatar Nevo1,Ephraim P.Lansky1,Rivka Ofir2,Anupam Bishaye e3

Aloe?s pharmaceutical potential, against neoplastic disease, anticancer biological mechanism of acemannan, pluripotent effector cells, aloe induce macrophage activating activity, immunobiology, Aloe polysaccharide, combined with chemotherapeutic agents, such as cisplatin (DDP) and 5-fluorouracil (5-FU), enhances the therapeutic effect and reduces adverse side effects, tablet, powder, capsule, granule, suspension, syrup, oral liquid, emulsion, nanoparticle, liposome, ointment, patch, and injection, stimulatory activity of PAC?I (acemannan polysaccharide) on murine peritoneal macrophages

Author: Womble D, Helderman JH.

antiviral agent with immune enhancement capabilities, cytotoxic T-lymphocyte (Tc) function, lymphocyte cultures, chromium release, alloantigen, allostimulation, T-cells, immune enhancing

Author: Sun?A Im, Young-Ran Lee, Young?Hee Lee, Myung-Koo Lee, Young In Park, Sungwon Lee, Kyungjae Kim, C. Lee

immunomodulatory component, Acemannan, a mixture of various length polymer chains of ?-(1,4)-linked acetylated galactomannan isolated from aloe vera, may be the best-characterized immunomodulatory polysaccharides, immunoaugmenting activities of acemannan are mediated through the activation of macrophages, Acemannan also augments hematopoiesis, induces maturation of immature dendritic cells, maximum immunomodulatory activity is between 5 kDa and 400 kDa;

Author Endang Diyah Ikasari*, Anang Budi Utomo, Hanny Setyowati, Salasa Ayu Trisnawati

Ranitidine hydrochloride is a competitive inhibitor of histamine H2receptors, drug of choice in the treatment of ulcer, The drug has a short biological half-life of approximately 2–3 hours, thus a sustained release dosage form of ranitidine HCl is desirable. The aim of this study was to formulate and in vitro evaluate microgranules with ranitidine HCl, Microgranules were prepared by the wet granulation method using aloe vera powder as bio adhesive polymer. Increasing concentration of aloe vera powder results decreasing of flow rate, improving of moisture content, swelling index, in vitro bio adhesive, and dissolution efficiency, results indicated that aloe vera powder is a suitable polymer for developing a sustained-release dosage form of ranitidine HCl for local delivery in the gastrointestinal tract, The polymers used in the mucoadhesive dosage form of ranitidine HCl are a combination of aloe vera polymer 27.34% and Carbopol 934P 7.62% , mucoadhesive microgranule of ranitidine HCl undergoes a slow drug release at pH 7.8 because the gel expands optimally so that the release rate of the drug can be controlled. Many factors that influence dissolution test in vitro include dissolution media

Author Endang Diyah Ikasari1*, Intan Martha Cahyani2

several factors that influence dissolution test in vitro such as dissolution media. The AIF media (Atrial Intestinal Fluid) and the SIF media (Simulated Intestinal Fluid) media are among the media that can be used in the dissolution test. Mucoadhesive microgranule of ranitidine HCl using a combination polymer of aloe vera powder and carbopol 934P that expands maximally at pH 7.8. The purpose of this study was to determine the dissolution profile of mucoadhesive microgranule of ranitidine HCl in AIF (Artificial Intestinal Fluid) pH 7.8 and SIF (Simulated Intestinal Fluid) pH 7.8 with a line of identification approach, the method of making granules used is wet granulation. Data analysis using Statistic Product and Service Solution (SPSS) 16.0 with Test, the test results showed that the dissolution profile of AIF media followed Higuchi model while in SIF media following release model of order 1. Mechanism of release of mucoadhesive microgranule of ranitidine HCl on SIF media was better than AIF media. Media type significantly influence dissolution test, Ranitidine is a class of Biopharmaceutics Classification System (BCS) class III which has high solubility and low permeability,

Authors J. Bland, D. Ph

effect of oral Aloe vera juice supplementation on gastric pH, stool specific gravity, protein digestion/absorption, and stool microbiology. Results indicate that supplemental oral Aloe vera juice is well tolerated by most individuals and has favorable effects upon a number of gastrointestinal parameters, A discussion of the potential role of Aloe vera juice on inflammatory bowel disorders, Aloe vera, when ingested orally, also has a systemic influence both on improvement of gastrointestinal function and possibly even other important physiological relationships. Individuals who have suffered from indigestion, irritable bowel syndrome, colitis, and excess acid stomach, have reported relief from these conditions by the oral administration of Aloe vera juice. The physiological effects of orally administered Aloe vera juice on gastrointestinal function has not been studied under controlled conditions. Such a study is essential to establish the role that orally administered Aloe vera juice plays in imparting favorable gastrointestinal functional changes, This study evaluates the impact of orally consumed Aloe vera juice on gastrointestinal function by evaluation of colonic bacterial activity, gastrointestinal pH, impact upon stool specific gravity, and gastrointestinal motility in normal subjects.

Author: C. Bender, S. Graziano, Benno F. Zimmerman, Helmut H. Weidlich

teas and herbal infusions, health promoters due to their content in antioxidant compounds, antioxidant capacities, through chemical and cellular assays, infusions and as ingredients in cosmetics products and in food formulations, protection against peroxyl radicals under physiological conditions, cell-based assay, cellular distribution and metabolism of the antioxidants

Author Brayden D J, O’Mahony D J.

drug delivery technology, injection, infusion or by subcutaneous implants, Oral delivery, intestinal site of absorption and the physico-chemical properties of the agent, these labile compounds can be successfully formulated for oral delivery using intestinal-protective-targeting- and epithelial-permeating approaches, drug delivery industry, novel oral formulations of agents, biotech products and delivery technology, controlled release oral forms, Drug reformulation (with or without specialized delivery devices), non-injectable routes of delivery, Peptide-based biotechnology products are subject to the same hostile environment encountered by all peptides in the gastrointestinal (GI)tract , factors (Box 2)are susceptibility to degradation by the acidic pH of the stomach, metabolism by luminal, brush border and cytosolic peptidases, and poor permeability across the intestinal epithelium because of size, charge and hydrophilicity, Physiological considerations, such as gastric transit time, dilution and interaction with intestinal debris, also influence peptide contact with the absorptive epithelium of the most appropriate-ate intestinal region, survival and delivery to the hepatic portal vein, first-pass metabolism as well as the entero-hepatic shunt, GI tract has evolved to break down dietary peptides and proteins into di-, tri- and quaternary amino acids, there is evidence to show that carefully designed peptide formulations, or even some natural soluble antigens, can be absorbed intact, albeit in low concentrations, addressing permeability issues, polar molecular surface area, permeability coefficients can be achieved in the chemical-design stages of synthesis, small or large changes in solubility or permeability of a particular molecule will make a significant difference to oral bioavailability, epithelial tight-junction opener, is approved as an excipient, effective absorption, transepithelial resistance was reduced and the flux of the paracellular marker, paracellular transport alone could not account for adequate and sustained absorption, chemical enhancers or surfactant-like agents, particulate formulation to receptor sites on the brush border of the intestine, Human cell culture monolayer models, small intestine , transcellular carrier-mediated transport, Caco-2 intestinal cell model, receptor expression patterns, intrinsic factor-dependent uptake, apical membrane receptor, capacity for transport across epithelia, proton-dependent dipeptide transporter

Author Junginger, H.E.; Verhoef, J.C.

low molecular weight transmucosal penetration enhancers for improved absorption of hydrophilic drugs (e.g. peptides and proteins), related mechanisms of action, novel types of macromolecular penetration enhancers, such as anionic polyacrylates and cationic chitosan and chitosan derivatives, have been developed. These polymers can enhance the paracellular permeability of mucosal epithelia (intestinal, nasal) by transiently opening the tight junctions, thereby increasing the paracellular absorption of hydrophilic and macromolecular drugs. Neither of these two classes of polymers interact with mucosal cell membrane components and consequently do not enhance transcellular transport of hydrophilic compounds, polyacrylates and chitosan derivatives show no acute toxicity and are not absorbed, these characteristics favor the conclusion that both types of polymers are safe penetration enhancers for transmucosal delivery of hydrophilic drugs and offer promising prospects for novel pharmaceutical applications, Cell membranes of the mucosal linings consist of phospholipid bilayers in which proteins for signal transfer are incorporated. These cell membranes are barriers to macromolecules and to most polar compounds, but they are relatively permeable to water and small hydrophobic molecules. Methods to facilitate transport of molecules, either small or large, across epithelial cells, Mechanisms of action of penetration enhancers (absorption promoters) can influence the mucosa in different ways: By acting on the mucous layer, By acting on the membrane components, By acting on the tight junctions, absorption enhancers are functional excipients included in formulations to improve the absorption of a pharmacologically active drug. The term absorption enhancer usually refers to an agent whose function is to increase absorption by enhancing membrane permeation, rather than increasing solubility, so such agents are sometimes more specifically termed permeation enhancers, advanced absorption enhancers currently in development and the formulation technologies, barriers to absorption and the mechanisms by which those barriers can be surmounted is presented. Factors influencing the success of absorption-enhancing formulations, absorption enhancement has also been applied to delivery by the transmucosal and transdermal routes, the agents and technologies are mainly those that alter drug permeation through the biological membrane that acts as the barrier to absorption, active ingredient is not chemically altered, but is combined with another agent or a specific formulation composition to increase permeability. Technologies that enhance absorption by increasing dissolution or solubility, absorption-enhancing technologies

Author Crowley PJ, Martini LG.

molecular biology, physiological and disease processes, improving the performance of a medication, kinetics and dynamics of drug action, dose–response relationships, improve efficacy or reduce side effects, properties of any drug, composite of the innate activity and properties of the compound as modulated by the formulation, clinical effectiveness, design of formulations, development of new agents, application of formulation technologies, resurrection of older molecules, improve absorption (intestinal, buccal and transdermal) and prolong therapeutic effects, significant clinical benefit, terms of effectiveness, safety or convenience, novel path forward, antibacterial agents

Author Jambwa T, Viljoen A, Hamman JH.

Aloe gel , Aloe whole leaf , Controlled release , Powder flow , Matrix type tablet, Swelling , Mucoadhesiveness, Disadvantages of conventional immediate release tablets include fluctuations of drug plasma levels over successive administrations and forgotten doses may result in larger fluctuations that increase the chance of side effects, emergence of resistance and/or treatment failure , modified release drug delivery system is capable of delivering the drug to the target site at a rate that is required by the therapeutic needs of the patient for the specified period of treatment , controlled release drug delivery system is one that specifically controls the release of the drug in such a way that constant drug levels are maintained in the systemic blood circulation, which usually requires delivery of the maintenance dose at a rate governed by zero-order kinetics, matrix-type tablet is considered as one of the most preferred controlled release dosage forms because they can be manufactured by cost-effective methods such as direct compression on a tablet press and the risk of dose-dumping is low, Mini-monolithic matrices are an attractive alternative for pellets or beads to be loaded into a single hard gelatin capsule to produce a multiple-unit dosage form with several advantages over single-unit dosage forms, Polymers used in dosage form design are often classified as synthetic, semi-synthetic and natural polymers, polysaccharides obtained from plant materials are often extracted from either mucilage (also referred to as gel) or gum. Many succulent plants such as those from the genus Aloe store water in the form of mucilage or gel-containing tissue in their leaves to survive under arid conditions, aloe barbadensis miller Acetylated polymannan (also referred to as acemannan or aloverose) is considered the main functional component of Aloe Vera Gel gel, which is a polysaccharide consisting of a long chain of acetylated mannose monomers , Since polysaccharide rich aloe leaf materials showed potential as excipients for the production of controlled release monolithic dosage forms, aloe species alone and in combination with other polymers as matrix forming agent, powder flowpropierties aloe vera 200 : 1 powder , Carbopol and hydroxypropyl methyl cellulose as well as combinations of each of the aloe materials with CBPL and HPMC in three different ratios (i.e. 25:75, 50:50, 75:25). The bulk and tapped densities of the powders were determined to calculate Carr’s index values as well as Hausner ratio values and the angle of repose values were measured to characterize the powders in terms of their flow properties, All bulk and tapped density tests were conducted using a mass of 33.3 g of each powder, which was poured into a 250 mL graduated glass measuring cylinder, Carr’s index (or percentage compressibility) and Hausner ratio values, Angle of repose, Composition of the mini-matrix type tablets, model drugs for this investigation that were included in the mini-matrix type tablets were: a freely soluble drug, diltiazem [(2S,3S)-3-acetyloxy-5-[2-dimethyl-amino]-2-(4-methoxyphenyl)-2,3-dihydro1,5-benzothiazepin-4(5H)-one hydrochloride] (particle size: 161 µm) and a poorly soluble drug, ibuprofen [2-(4-isobutylphenyl)-propionic acid] (particle size: 28 µm), powders and combinations of powders as described for the powder flow property measurements, formulations of the mini-matrix type tablets, which each included ibuprofen or diltiazem as a model drug compound. These formulations were prepared by mixing the ingredients for direct compression, however, the aloe materials with poor flow properties were dry granulated first and then compressed with 6 mm concave punches on a multi-station rotary press (Cadmach CM 03-16), his relatively small tablet diameter was chosen to produce matrix type tablets that can be loaded into size 0 hard gelatin capsules to produce mini-tablet-in-capsule systems , mini-tablet-in-capsule systems, compressibility into acceptable tablets, laminate or cap or stick to the punches, mini-matrix type tablets were characterized in terms of their physical properties, mucoadhesive properties, swelling behavior and dissolution kinetics, e weight variation test, Hardness and friability, Erkewa hardness tester, tablet was placed between two anvils, force is applied and the crushing strength, mini-matrix type tablets involved the measurement of the force required to detach a mini-tablet from the mucosal surface of excised pig intestine with a TA.XT plus texture analyser, swelling of the mini-matrix type tablets, dissolution study, Kinetic analysis of drug release data, bulk density, tapped density, Carr’s index and Hausner ratio values, Angle of repose and flow rate, funnel, powders containing Aloe vera gel material alone as well as in combination with hydroxypropyl methyl cellulose have excellent flow (i.e. having an angle of repose below 20), g Aloe Vera Gel gel and A. ferox gel alone and in combination with other polymers exhibited very good flow properties according to the flow rate values (lower flow rate values indicate faster flow through the funnel), powder flowability, physical properties of the mini-matrix type tablets, hardness, friability and mass variation, bulk and tapped densities, Mucoadhesive properties of the mini-matrix type tablets, mucosal Surface, intestinal tissue, Carbopol, which is a known mucoadhesive polymer, Aloe Vera Gel whole leaf was combined with hydroxypropyl methyl cellulose in a tablet formulation it increased the mucoadhesion of the hydroxypropyl methylcellulose, angle of repose and flow rate results indicated that Aloe Vera Gel gel powder has excellent powder flowability, Aloe vera extract also showed very good powder flow properties based on the angle of repose value, aloe powder flow results it was expected that out of all the aloe materials investigated Aloe Vera Gel gel extract would be good candidates for direct compression into tablet, Aloe Vera Gel gel and Aloe Vera Gel whole leaf extract could be directly compressed into mini-matrix type tablets when used alone as excipients, individual aloe materials that could be compressed into minimatrix type tablets showed relatively fast erosion and disintegration and therefore could be used to form immediate release tablets by means of direct compression,Aloe vera gel in combination with Carbopol showed swelling and the drug release approached zero order kinetics indicating that this aloe material is a good candidate for use as an excipient in matrix type tablets for modified drug release.

Author Toliopoulos I, Simos Y, Verginadis I, et al.

scientific investigation taking place into the function and the mechanisms of action of natural killer (NK) cells (NKCs), plant extracts and vitamin supplements may play an immunoregulatory role by stimulating the functionality of the NKCs,

Author: Ningyang Lia1 Chaofan Wanga1 Milen I.Georgievbc Vivek K. Bajpaid Rosa Tundise Jesus Simal-Gandaraf Xiaoming LuaJianbo XiaofXiaozhen Tanga Xuguang Qiao

dietary polysaccharides as anticancer agents, nutritious dietary supplements, side effect-free therapeutics, biomacromolecules, Natural anticancer polysaccharides, physicochemical properties

Author Agnieszka Kosinska, Wilfried Andlauer

Tight junction, Epithelial barrier modulation, Phenolic compounds, Paracellular transport, Food components, primary function of the human intestine is to absorb nutrients and water, important is its ability to act as a selective barrier to protect the human system. Intestinal epithelium is formed by a monolayer of epithelial cells. Adjacent cells of the monolayer are sealed together by the formation of tight junctions (TJs)–complex protein systems. The structure of TJ involves transmembrane proteins linked to a cytoplasmic plaque, which is formed by a network of scaffolding and adaptor proteins, signalling components and actin-binding cytoskeleton linkers. TJs regulate paracellular transport of compounds as well as physical barrier function of epithelium, which is linked to pathogenesis of inflammatory bowel disease, ulcerative colitis, Crohn’s disease and food allergies. Epithelium is intensively exposed to food components, The targeted usage of food components to modulate TJ permeability is of vital importance for enhancing the absorption of poorly permeable drugs or bioactive compounds and, on the other hand, for sealing the junction in order to limit the risk of intestine pathology

Author: Suwimon Jettanacheawchankit 1, Siriruk Sasithanasate, Polkit Sangvanich, Wijit Banlunara, Pasutha Thunyakitpisal

wound healing, Gingival fibroblasts (GFs) play an important role in oral wound healing, acemannan, a polysaccharide extracted from Aloe vera gel, keratinocyte growth factor-1 (KGF-1), vascular endothelial growth factor (VEGF), and type I collagen production, cell proliferation, type I collagen expressions, extracellular matrix, herbal medicine , Aloe vera (Aloe barbadensis MILLER, healing skin wounds, Acemannan, ?-(1,4)-acetylated polymannose is the major polysaccharide of Aloe vera gel, exerts an immunostimulative effect by activating macrophages, precise coordination of connective tissue repair, re-epithelialization, and angiogenesis, generate new tissue.

Author Z Zheng, X Pan, L Luo, Q Zhang, X Huang, Y Liu

Polysaccharides have been widely used as biomaterials and drugs after oral administration due to their suitable physicochemical properties, good bioactivities and low toxicities, pharmacokinetics and absorption mechanism, oral administration, polysaccharide detection technologies such as immunoassays, fluorescent and isotopic labelling, the oral pharmacokinetics of polysaccharides, paracellular pathway, transcellular pathways and M cell-mediated transport were analyzed as mechanisms for oral absorption. The potential factors affecting the oral absorption of polysaccharides, including their charge, molecular weight, spatial structure and dose, as well as the species and physiological state of organisms, were analyzed. Based on the absorption mechanism and influencing factors, we look forward to further investigating possible strategies for improving the oral absorption of polysaccharides, cell Microfold, cell Mw Molecular weight, TJ Tight junction 99mTc99m-technetium HA Hyaluronan SIPS quid ink polysaccharide FTSC Fluorescein-5-thiosemicarbazide TEER Transepithelial electrical resistance GFP Grifola frondosa polysaccharide APTSAminopyrene-1,3,6-trisulfonate LBP Lycium barbarum polysaccharide SCLPS milax china L. polysaccharide PM Polymannuronic acid PG Polyguluronic acid GALT Gut-associated lymphoid tissue DTAF5-(4,6-Dichlorotriazinyl) aminofluorescein TMCN-trimethyl chitosan Cmax Maximum plasma concentrationFDFITC-dextranLMWHLow molecular weight heparinDOCADeoxycholic acid AUC Area under the curve BAT Bile acid transport GLP Ganoderma lucidum polysaccharide PL Phospholipids LMWCS Low molecular weight chondroitin sulfate?-LNA?-Linolenic acid GSH Glutathione OJP Ophiopogon japonicus polysaccharide CCP Coptis chinensis Franch polysaccharide SNAD Sodium N-[10-(2-hydroxybenzoyl) amino] decanoate SNAC Sodium N-[8-(2-hydroxybenzoyl) amino] caprylate APSAstragalus polysaccharidesaPTTActivated partial thromboplastin time

Author: Ram Kumar Sahua Jiyauddin Khanb

Poorly water-soluble drug, approximately 60–70% of the drug molecules are insufficiently soluble in aqueous media and/or have very low permeability to allow for their adequate and reproducible absorption from the gastrointestinal tract (GIT) following oral administration, Formulation scientists have to adopt various strategies to enhance their absorption, self-emulsifying systems, scientists to transform the liquid self-emulsifying drug delivery systems (SEDDS) to solid-SEDDS by adsorption, spray drying, lyophilization, melt granulation, extrusion, and so forth to formulate various dosage forms like self-emulsifying capsules, tablets, controlled release pellets, beads, microspheres, nanoparticles, suppositories, implants, deliver new drug molecules with enhanced bioavailability mostly exhibiting poor aqueous solubility, It is estimated that between 40% and 70% of all new chemical entities identified in drug discovery programs are insufficiently soluble in aqueous media, the increase in the proportion of poorly soluble candidates is frequently attributed to improvements in synthesis technology, which has enabled the design of very complicated compounds, and a change in discovery strategy from a so-called phenotypic approach to a target-based approach, Various physicochemical properties which contribute to the poor solubility of various drugs include their complex structure, size, high molecular weight, high lipophilicity, compound H-bonding to solvent, intramolecular H-bonding, intermolecular H-bonding (crystal packing), crystallinity, polymorphic forms, ionic charge status, pH, and salt form, drug for absorption can be enhanced by formulation of the drug as a solubilized within a colloidal dispersion, hydrophobic drugs is well documented in the literature. These generally consist of a drug dissolved in a blend of excipients (5 classes of excipients) with wide variety of physicochemical properties ranging from pure triglyceride oils, mono- and diglycerides, and substantial proportion of lipophilic or hydrophilic surfactants and cosolvents, enhanced oral bioavailability enabling reduction in dose, more consistent temporal profiles of drug absorption, selective targeting of drug(s) toward specific absorption window in GIT, and protection of drug(s) from the hostile environment in gut, Types of Self-Emulsifying Systems: Self-Emulsifying, Self-Microemulsifying, and Self-Nanoemulsifying Drug Delivery System, unit dosage form in soft or hard gelatin capsules due to the anhydrous nature, increase the intestinal permeability and minimize the effect of pH on drug absorption, degree of participation of the portal venous and mesenteric lymphatic pathways in overall drug absorption, Selection of Excipients in Self-Emulsifying Formulations, surfactants may improve the affinity between lipids and intestinal membrane or increase the permeability of the intestinal membrane. Surfactants increase the permeability by partitioning into the cell membrane and disrupting the structural organization of the lipid bilayer leading to permeation enhancement, most drugs are absorbed via the passive transcellular route, absorption enhancing effects by increasing the dissolution rate of the drug, avoid amount of solidifying excipients may affect the release of the drug, nature of the excipients used may affect the drug absorption, probability of irreversible phase separation on reconstitution, clogging of spray nozzles due to oil content in spray-drying method, degradation of drug during solidification process, reduction in drug loading capacity, difficulty in ensuring content uniformity, (8) Probability of residual solvents used during granulation, Capsule filling is the simplest and the most common technology for the encapsulation of liquid, semisolid, or solid SE formulations for the oral route, aloe vera gel can help in unfavourable physicochemical properties for their drug absorption in the body

Author Toliopoulos I, Simos Y, Verginadis I, et al.

scientific investigation taking place into the function and the mechanisms of action of natural killer (NK) cells (NKCs), plant extracts and vitamin supplements may play an immunoregulatory role by stimulating the functionality of the NKCs,

Author J. Hochman, P. Artursson

therapeutic agents to exert their pharmacological effects, cross the biological membranes into the systemic circulation and reach the site of action, Drugs cross the membranes by one of two pathways; paracellular or transcellular, drugs are transported transcellularly, physiocochemical properties, The paracellular pathway is governed by the tight junctions, absorption enhancers for paracellular drug transport enhancement, drug delivery improvement, tight junctions are a multiple unit structure composed of multiprotein complex , drugs across the intestinal epithelium and the blood brain barrier endothelium, mucosal adjuvant, drug delivery of therapeutic agents.

Author: Carla Pereira, J. Costa, B. Sarmento, Francisca Araújo

oral administration of drugs is still a huge challenge because of the harsh conditions of the gastrointestinal tract, drug design and development, permeability behavior of those drugs are essential to improve the drug delivery field, Caco-2 model has been the gold-standard in vitro method used for such purposes

Author: Choi S, Chung MH.

Aloe barbadensis Miller, immunomodulatory, antiinflammatory, UV protective, antiprotozoal, and wound- and burn-healing promoting properties, relationships between the components of aloe vera and their pharmacologic effects, promote wound, burn, and frost-bite healing, in addition to having antiinflammatory, antifungal, hypoglycemic, and gastroprotective properties, Wound healing is considered to be composed of three overlapping events: inflammation, new tissue formation, and matrix remodeling, Aloe vera gel extract stimulated fibroblast growth in a synovial model and also enhanced wound tensile strength and collagen turnover in wound tissue, topical application of aloe vera gel stimulated fibroblast activity and collagen proliferation, in addition to increasing the content of granulation tissue and tissue crosslinking by increasing the aldehyde content and decreasing the acid solubility, aloe vera gel increased levels of hyaluronic acid and dermatan sulphate in granulation tissue, formation of new tissue, angiogenesis is essentially required to provide oxygen and metabolites to the tissues. An increase in the blood supply was observed after aloe vera gel treatment, and it has been suggested that an increased oxygen access is one of the factors enhanced by aloe vera gel

Author: Crowley PJ, Martini LG.

molecular biology, physiological and disease processes, improving the performance of a medication, kinetics and dynamics of drug action, dose–response relationships, improve efficacy or reduce side effects, properties of any drug, composite of the innate activity and properties of the compound as modulated by the formulation, clinical effectiveness, design of formulations, development of new agents, application of formulation technologies, resurrection of older molecules, improve absorption (intestinal, buccal and transdermal) and prolong therapeutic effects, significant clinical benefit, terms of effectiveness, safety or convenience, novel path forward, antibacterial agents

Author: Jambwa T, Viljoen A, Hamman JH.

Aloe gel , Aloe whole leaf , Controlled release , Powder flow , Matrix type tablet, Swelling , Mucoadhesiveness, Disadvantages of conventional immediate release tablets include fluctuations of drug plasma levels over successive administrations and forgotten doses may result in larger fluctuations that increase the chance of side effects, emergence of resistance and/or treatment failure , modified release drug delivery system is capable of delivering the drug to the target site at a rate that is required by the therapeutic needs of the patient for the specified period of treatment , controlled release drug delivery system is one that specifically controls the release of the drug in such a way that constant drug levels are maintained in the systemic blood circulation, which usually requires delivery of the maintenance dose at a rate governed by zero-order kinetics, matrix-type tablet is considered as one of the most preferred controlled release dosage forms because they can be manufactured by cost-effective methods such as direct compression on a tablet press and the risk of dose-dumping is low, Mini-monolithic matrices are an attractive alternative for pellets or beads to be loaded into a single hard gelatin capsule to produce a multiple-unit dosage form with several advantages over single-unit dosage forms, Polymers used in dosage form design are often classified as synthetic, semi-synthetic and natural polymers, polysaccharides obtained from plant materials are often extracted from either mucilage (also referred to as gel) or gum. Many succulent plants such as those from the genus Aloe store water in the form of mucilage or gel-containing tissue in their leaves to survive under arid conditions, aloe barbadensis miller Acetylated polymannan (also referred to as acemannan or aloverose) is considered the main functional component of Aloe Vera Gel gel, which is a polysaccharide consisting of a long chain of acetylated mannose monomers , Since polysaccharide rich aloe leaf materials showed potential as excipients for the production of controlled release monolithic dosage forms, aloe species alone and in combination with other polymers as matrix forming agent, powder flowpropierties aloe vera 200 : 1 powder , Carbopol and hydroxypropyl methyl cellulose as well as combinations of each of the aloe materials with CBPL and HPMC in three different ratios (i.e. 25:75, 50:50, 75:25). The bulk and tapped densities of the powders were determined to calculate Carr’s index values as well as Hausner ratio values and the angle of repose values were measured to characterize the powders in terms of their flow properties, All bulk and tapped density tests were conducted using a mass of 33.3 g of each powder, which was poured into a 250 mL graduated glass measuring cylinder, Carr’s index (or percentage compressibility) and Hausner ratio values, Angle of repose, Composition of the mini-matrix type tablets, model drugs for this investigation that were included in the mini-matrix type tablets were: a freely soluble drug, diltiazem [(2S,3S)-3-acetyloxy-5-[2-dimethyl-amino]-2-(4-methoxyphenyl)-2,3-dihydro1,5-benzothiazepin-4(5H)-one hydrochloride] (particle size: 161 µm) and a poorly soluble drug, ibuprofen [2-(4-isobutylphenyl)-propionic acid] (particle size: 28 µm), powders and combinations of powders as described for the powder flow property measurements, formulations of the mini-matrix type tablets, which each included ibuprofen or diltiazem as a model drug compound. These formulations were prepared by mixing the ingredients for direct compression, however, the aloe materials with poor flow properties were dry granulated first and then compressed with 6 mm concave punches on a multi-station rotary press (Cadmach CM 03-16), his relatively small tablet diameter was chosen to produce matrix type tablets that can be loaded into size 0 hard gelatin capsules to produce mini-tablet-in-capsule systems , mini-tablet-in-capsule systems, compressibility into acceptable tablets, laminate or cap or stick to the punches, mini-matrix type tablets were characterized in terms of their physical properties, mucoadhesive properties, swelling behavior and dissolution kinetics, e weight variation test, Hardness and friability, Erkewa hardness tester, tablet was placed between two anvils, force is applied and the crushing strength, mini-matrix type tablets involved the measurement of the force required to detach a mini-tablet from the mucosal surface of excised pig intestine with a TA.XT plus texture analyser, swelling of the mini-matrix type tablets, dissolution study, Kinetic analysis of drug release data, bulk density, tapped density, Carr’s index and Hausner ratio values, Angle of repose and flow rate, funnel, powders containing Aloe vera gel material alone as well as in combination with hydroxypropyl methyl cellulose have excellent flow (i.e. having an angle of repose below 20), g Aloe Vera Gel gel and A. ferox gel alone and in combination with other polymers exhibited very good flow properties according to the flow rate values (lower flow rate values indicate faster flow through the funnel), powder flowability, physical properties of the mini-matrix type tablets, hardness, friability and mass variation, bulk and tapped densities, Mucoadhesive properties of the mini-matrix type tablets, mucosal Surface, intestinal tissue, Carbopol, which is a known mucoadhesive polymer, Aloe Vera Gel whole leaf was combined with hydroxypropyl methyl cellulose in a tablet formulation it increased the mucoadhesion of the hydroxypropyl methylcellulose, angle of repose and flow rate results indicated that Aloe Vera Gel gel powder has excellent powder flowability, Aloe vera extract also showed very good powder flow properties based on the angle of repose value, aloe powder flow results it was expected that out of all the aloe materials investigated Aloe Vera Gel gel extract would be good candidates for direct compression into tablet, Aloe Vera Gel gel and Aloe Vera Gel whole leaf extract could be directly compressed into mini-matrix type tablets when used alone as excipients, individual aloe materials that could be compressed into minimatrix type tablets showed relatively fast erosion and disintegration and therefore could be used to form immediate release tablets by means of direct compression,Aloe vera gel in combination with Carbopol showed swelling and the drug release approached zero order kinetics indicating that this aloe material is a good candidate for use as an excipient in matrix type tablets for modified drug release.

Author Agnieszka Kosinska, Wilfried Andlauer

Tight junction, Epithelial barrier modulation, Phenolic compounds, Paracellular transport, Food components, primary function of the human intestine is to absorb nutrients and water, important is its ability to act as a selective barrier to protect the human system. Intestinal epithelium is formed by a monolayer of epithelial cells. Adjacent cells of the monolayer are sealed together by the formation of tight junctions (TJs)–complex protein systems. The structure of TJ involves transmembrane proteins linked to a cytoplasmic plaque, which is formed by a network of scaffolding and adaptor proteins, signalling components and actin-binding cytoskeleton linkers. TJs regulate paracellular transport of compounds as well as physical barrier function of epithelium, which is linked to pathogenesis of inflammatory bowel disease, ulcerative colitis, Crohn’s disease and food allergies. Epithelium is intensively exposed to food components, The targeted usage of food components to modulate TJ permeability is of vital importance for enhancing the absorption of poorly permeable drugs or bioactive compounds and, on the other hand, for sealing the junction in order to limit the risk of intestine pathology

Author: Brayden D J, O’Mahony D J.

drug delivery technology, injection, infusion or by subcutaneous implants, Oral delivery, intestinal site of absorption and the physico-chemical properties of the agent, these labile compounds can be successfully formulated for oral delivery using intestinal-protective-targeting- and epithelial-permeating approaches, drug delivery industry, novel oral formulations of agents, biotech products and delivery technology, controlled release oral forms, Drug reformulation (with or without specialized delivery devices), non-injectable routes of delivery, Peptide-based biotechnology products are subject to the same hostile environment encountered by all peptides in the gastrointestinal (GI)tract , factors (Box 2)are susceptibility to degradation by the acidic pH of the stomach, metabolism by luminal, brush border and cytosolic peptidases, and poor permeability across the intestinal epithelium because of size, charge and hydrophilicity, Physiological considerations, such as gastric transit time, dilution and interaction with intestinal debris, also influence peptide contact with the absorptive epithelium of the most appropriate-ate intestinal region, survival and delivery to the hepatic portal vein, first-pass metabolism as well as the entero-hepatic shunt, GI tract has evolved to break down dietary peptides and proteins into di-, tri- and quaternary amino acids, there is evidence to show that carefully designed peptide formulations, or even some natural soluble antigens, can be absorbed intact, albeit in low concentrations, addressing permeability issues, polar molecular surface area, permeability coefficients can be achieved in the chemical-design stages of synthesis, small or large changes in solubility or permeability of a particular molecule will make a significant difference to oral bioavailability, epithelial tight-junction opener, is approved as an excipient, effective absorption, transepithelial resistance was reduced and the flux of the paracellular marker, paracellular transport alone could not account for adequate and sustained absorption, chemical enhancers or surfactant-like agents, particulate formulation to receptor sites on the brush border of the intestine, Human cell culture monolayer models, small intestine , transcellular carrier-mediated transport, Caco-2 intestinal cell model, receptor expression patterns, intrinsic factor-dependent uptake, apical membrane receptor, capacity for transport across epithelia, proton-dependent dipeptide transporter

Author: Junginger, H.E.; Verhoef, J.C.

penetration enhancers poly(acrylates) chitosan N-trimethyl chitosan mucosal membrane barriers transport mechanisms tight junctions hydrophilic drugs peptides proteins, low molecular weight transmucosal penetration enhancers for improved absorption of hydrophilic drugs, novel types of macromolecular penetration enhancers, such as anionic polyacrylates and cationic chitosan and chitosan derivatives, have been developed, enhance the paracellular permeability of mucosal epithelia (intestinal, nasal) by transiently opening the tight junctions, transmucosal delivery of hydrophilic drugs

Author: Coviello, T.; Matricardi, P.; Marianecci, C.; Alhaique, F.

Hydrogels are three-dimensional, hydrophilic, polymeric networks, with chemical or physical cross-links, capable of imbibing large amounts of water or biological fluids. Among the numerous macromolecules that can be used for hydrogel formation, polysaccharides are extremely advantageous compared to synthetic polymers being widely present in living organisms and often being produced by recombinant DNA techniques, Polysaccharides are usually non-toxic, biocompatible and show a number of peculiar physico-chemical properties that make them suitable for different applications in drug delivery systems, techniques used for the hydrogel network preparation, on the drug delivery results, on clinical applications as well as on the possible use of such systems as scaffolds for tissue engineering, hydrogels are three-dimensional, hydrophilic, polymeric networks capable of imbibing large amounts of water or biological fluid, These networks can be classified into two main categories according to the type of cross-linking among the macromolecules, whether chemically or physically based, however, it should be pointed out that both chemical and physical cross-links can occur in the same hydrogel network, In their ability to retain a significant amount of water, hydrogels are quite similar to natural living tissues, rendering them useful for a wide variety of biomedical applications, use of hydrogels as matrices for the encapsulation of living cells, as biologically friendly scaffolds for tissue engineering and for the controlled release of proteins, hydrogels suitable as delivery systems, formulation of modified release dosage forms and devices

Author: J. Hochman, P. Artursson

therapeutic agents to exert their pharmacological effects, cross the biological membranes into the systemic circulation and reach the site of action, Drugs cross the membranes by one of two pathways; paracellular or transcellular, drugs are transported transcellularly, physiocochemical properties, The paracellular pathway is governed by the tight junctions, absorption enhancers for paracellular drug transport enhancement, drug delivery improvement, tight junctions are a multiple unit structure composed of multiprotein complex , drugs across the intestinal epithelium and the blood brain barrier endothelium, mucosal adjuvant, drug delivery of therapeutic agents.

Author: Antoni FG, Pablo S, Susana S, Carmen R.

bioactive polysacharide, cell wall polysaccharides, aloe parenchyma tissues, Pectic polysaccharides, bioactivity

Author Pereira, R. F., Carvalho, A., Gil, M. H., Mendes, A., & Bartolo, P. J.,

Hydrogel films composed of alginate and Aloe vera gel were developed for wound healing applications, Films with different formulations can be prepared for the different phases of the wound healing process, Aloe vera gel significantly improves the water absorption and the in vitro degradation properties of alginate hydrogel films, the properties of the hydrogel films can be tailored by changing the Aloe vera content, this study investigates the influence of Aloe vera on water absorption and the in vitro degradation rate of Aloe vera-Ca-alginate hydrogel films, for wound healing and drug delivery applications, the influence of Aloe Vera Gel content (5%, 15% and 25%, v/v) on water absorption was evaluated by the incubation of the films into a 0.1 M HCl solution (pH 1.0), acetate buffer (pH 5.5) and simulated body fluid solution (pH 7.4) during 24 h. Results show that the water absorption is significantly higher for films containing high Aloe Vera Gel contents (15% and 25%), while no significant differences are observed between the alginate neat film and the film with 5% of Aloe Vera Gel, in vitro enzymatic degradation tests indicate that an increase in the Aloe Vera Gel content significantly enhances the degradation rate of the films. Control films, incubated in a simulated body fluid solution without enzymes, are resistant to the hydrolytic degradation, exhibiting reduced weight loss and maintaining its structural integrity. Results also show that the water absorption and the in vitro degradation rate of the films can be tailored by changing the Aloe Vera Gel content.

Author Z Zheng, X Pan, L Luo, Q Zhang, X Huang, Y Liu

Polysaccharides have been widely used as biomaterials and drugs after oral administration due to their suitable physicochemical properties, good bioactivities and low toxicities, pharmacokinetics and absorption mechanism, oral administration, polysaccharide detection technologies such as immunoassays, fluorescent and isotopic labelling, the oral pharmacokinetics of polysaccharides, paracellular pathway, transcellular pathways and M cell-mediated transport were analyzed as mechanisms for oral absorption. The potential factors affecting the oral absorption of polysaccharides, including their charge, molecular weight, spatial structure and dose, as well as the species and physiological state of organisms, were analyzed. Based on the absorption mechanism and influencing factors, we look forward to further investigating possible strategies for improving the oral absorption of polysaccharides, cell Microfold, cell Mw Molecular weight, TJ Tight junction 99mTc99m-technetium HA Hyaluronan SIPS quid ink polysaccharide FTSC Fluorescein-5-thiosemicarbazide TEER Transepithelial electrical resistance GFP Grifola frondosa polysaccharide APTSAminopyrene-1,3,6-trisulfonate LBP Lycium barbarum polysaccharide SCLPS milax china L. polysaccharide PM Polymannuronic acid PG Polyguluronic acid GALT Gut-associated lymphoid tissue DTAF5-(4,6-Dichlorotriazinyl) aminofluorescein TMCN-trimethyl chitosan Cmax Maximum plasma concentrationFDFITC-dextranLMWHLow molecular weight heparinDOCADeoxycholic acid AUC Area under the curve BAT Bile acid transport GLP Ganoderma lucidum polysaccharide PL Phospholipids LMWCS Low molecular weight chondroitin sulfate?-LNA?-Linolenic acid GSH Glutathione OJP Ophiopogon japonicus polysaccharide CCP Coptis chinensis Franch polysaccharide SNAD Sodium N-[10-(2-hydroxybenzoyl) amino] decanoate SNAC Sodium N-[8-(2-hydroxybenzoyl) amino] caprylate APSAstragalus polysaccharidesaPTTActivated partial thromboplastin time

Author: Antoni Femenia, Emma S.Sánchez, Susana Simal Carmen Rosselló

acetylated mannose-rich polymer that functions as storage polysaccharide, and a galacturonic acid-rich polymer as the main component comprising the cell walls of the parenchymatous tissue,

Author Tai-Nin Chow J, Williamson DA, Yates KM, Goux WJ.

Acemannan, an acetylated ?-1,4-linked glucomannan, Aloe vera gel carbohydrate, act as an immunostimulant, displaying adjuvant activity on specific antibody production [15] and enhancing the release of interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis fator-? (TNF-?) and interferon-? (INF-?) [22], Release of these cytokines stimulates an increase of up to 300% in the replication of fibroblasts in tissue culture and enhances macrophage phagocytosis, Proliferation of fibroblasts is known to be responsible for healing burns, ulcers and other wounds of the skin and gastrointestinal lining, adjuvant activity on specific antibody production, Carbohydrate composition, glycans, ability to activate macrophages and T cells

Author Tarkase K. N. and Danve V., Padmashree Dr. Vitthalrao Vikhe

achieve successful delivery of drug locally as well as systematically, rectal route, research, formulate and evaluate herbal extract Aloe Vera suppositories, Suppositories are inserted directly into the rectum to distribute their herbal powder to internal areas. Aloe Vera contains aloin, which is an anthraquinones glycoside. Aloin has been used as a laxative for constipation, laxative action, Suppositories of polyethylene glycol-l (PEG) 4000 and surfactant showed better permeation of drug and laxative action, Suppositories are designed for insertion into body cavities where they melt, soften or dissolve and exert local or systemic effects, the suppositories serve as an alternate where oral administration of drug is not suitable as in infants or patients suffering from nausea, vomiting and gastrointestinal disturbances, they provide the advantage that biotransformation of drugs in liver, pH conditions and gastrointestinal enzymes are avoided, suppository base play vital role in the release of medicament they hold the drug. The important property of suppository base is that it should remain solid at room temperature but soften, melt or dissolve readily at body temperature so that the drug is released after its administration, Herbal Suppositories of Aloe Vera can be used in patients suffering from nausea, gastric ulcers, comatose patients, geriatrics where administration is difficult or not possible through oral route. Studies have showed that the release characteristic of suppositories depends on the physicochemical properties of the drug, its carrier (suppository base) and surfactants, the particle size of drug and chemical composition increase or decrease the rate of release

Author Rachana Sharma

Drug delivery, Controlled drug delivery, Nanotechnology, Increasing interest in this area has been focused on controlled drug delivery using biocompatible polymers as carriers in recent years and aloe gel is an example of such category. Its ease of extraction and processing has made it possible to be used as nano drug carrier. Aloe gel has been reported to be used in successful and controlled delivery of Aspirin and Vitamin C. It has bright future in drug delivery because of its abundance and varieties available throughout the world. The aim of the present work is to evaluate the importance, effectiveness, and future prospect of a medicinal aromatic plant aloe vera in the field of nano drug delivery, traditional use of excipients in drug formulations was to act as inert vehicles to provide necessary weight, consistency and volume for the correct administration of the active ingredient, but in modern pharmaceutical dosage forms they often fulfill multi-functional roles such as modifying release, improvement of the stability and bioavailability of the active ingredient, enhancement of patient acceptability and ensure ease of manufacture. New and improved excipients continue to be developed to meet the needs of advanced drug delivery systems .These excipients or drug carriers may be in the form of biopolymers such as polysaccharides, proteins, lipids etc. which may be of plant origin or animal origin (for eg. Alginates, Chitosan, Pullulan ,Aloe gel etc.) or some synthetic biodegradable polymers. In current work the emphasis is given on the structure, properties and uses of aloe vera as nano drug carrier in modern and herbal nanotechnology,

Authors Morné Fouché, Jan Steenekamp, Hannlie Hamman , Josias Hamman

many active pharmaceutical ingredients (APIs) exhibit poor solubility and low dissolution rates in aqueous environments such as the luminal fluids of the gastrointestinal tract, oral bioavailability of these compounds is usually very low as a result of their poor solubility properties, formulation strategies to improve their aqueous solubility and dissolution rates, , or specialized dosage forms can be formulated that improve dissolution rate through various mechanisms, selected excipients (e.g., alkalinizing agents, surfactants and sugars), specialized dosage forms such as self-emulsifying delivery systems and formulation techniques such as inclusion complexes and solid dispersions, drug solubility and bioavailability enhancement, specialized dosage forms such as self-emulsifying delivery systems and formulation techniques such as inclusion complexes and solid dispersions, pharmacologically active compounds or drugs (also referred to as active pharmaceutical ingredients; APIs) are usually not administered to patients on their own as single compounds, but are formulated into carefully designed dosage forms, Pharmaceutical dosage forms provide a platform for repeatable accurate dosing, quality, efficacy, safety, stability as well as high patient acceptance and compliance, dosage forms were made by simply adding pharmacologically inert substances (also referred to as excipients) to the API to make up the required volume of an acceptable dosing unit, selection and production of excipients that fulfil specific functions, beyond just making up volume, such as assisting in production of the dosage form and optimizing drug delivery from novel dosage forms, stability of the API, dose uniformity, effective delivery of the API to the systemic circulation after administration as well as acceptable organoleptic properties, excipients are 90% of the total mass/volume of medicinal products, different classes of pharmaceutical excipients have different requirements in terms of safety evaluation, updates on regulatory requirements for pharmaceutical excipients are continuously introduced worldwide to ensure the safety of patients, multifunctional excipients’ refer to excipients (which can be co-processed for example) that fulfil multiple roles in a dosage form or drug delivery system, for example a direct-compressible filler material that also functions as a binder and/or disintegrant, high functionality excipients’ refers to a single excipient that provides additional functions to innovative drug delivery systems to improve the overall performance of the product with significant economic benefits, high functionality excipient is one that can provide better flow, act as a disintegrant and simultaneously allow a higher drug loading in the dosage form due to its high compressibility, 40% of current medication dispensed to patients in pharmacies exhibit relatively poor aqueous solubility properties, 90% of newly discovered therapeutic compounds in the development phase exhibit poor aqueous solubility, future research regarding the identification of solubility-enhancing excipients is of cardinal importance, functional excipients are needed to assist in overcoming their poor physico-chemical properties, Specialty excipients are used to produce dosage forms that can reduce the number of doses by modifying the rate of drug release or improve drug delivery by targeting drug release in a specific region in the gastrointestinal tract where drug absorption is the highest. Functional excipients are also used to re-formulate existing drugs in order to produce more effective products that are more cost-effective, a drug that exhibits an aqueous solubility lower than 0.1 mg per mL is likely to experience limited bioavailability, and its rate of absorption will be governed by the dissolution rate, Physico-chemical techniques that have been employed to improve the solubility of these drugs include formation of pro-drugs, formation of salts, co-precipitation, solvent evaporation and size reduction (or micronization), Formulation strategies that have been investigated for the same purpose include melt extrusion/granulation, formation of solid dispersions and formation of inclusion complexes. Furthermore, excipients such as surfactants, polymers, super-disintegrants and multifunctional fillers have been included in dosage forms to increase the apparent solubility of drugs, term ‘complex formation’ or ‘complexation’ refers to the binding of two or more individual molecules to form a combined chemical product, which act as a single chemical unit, dosage forms include conventional immediate release tablets, orally disintegrating tablets, effervescent tablets, and modified release dosage forms including slow release or sustained release drug delivery system, excipients that can increase an API’s solubility and dissolution rate include cyclodextrins, disintegrants, pH-adjusting excipients, natural polymers, surfactants, co-surfactants, oils/lipids and sugars, special interest to determine the clinical significance or value of formulation approaches on drug bioavailability and if they could result in decreasing the dose needed to reach effective blood plasma levels, Identifying the correct formulation method and using the suitable excipient in relation to the API may result in efficient pharmacological treatment by means of administrating a lower dose, which may have a significant cost implication.

Author: Morné Fouché, Jan Steenekamp, Hannlie Hamman , Josias Hamman

many active pharmaceutical ingredients (APIs) exhibit poor solubility and low dissolution rates in aqueous environments such as the luminal fluids of the gastrointestinal tract, oral bioavailability of these compounds is usually very low as a result of their poor solubility properties, formulation strategies to improve their aqueous solubility and dissolution rates, , or specialized dosage forms can be formulated that improve dissolution rate through various mechanisms, selected excipients (e.g., alkalinizing agents, surfactants and sugars), specialized dosage forms such as self-emulsifying delivery systems and formulation techniques such as inclusion complexes and solid dispersions, drug solubility and bioavailability enhancement, specialized dosage forms such as self-emulsifying delivery systems and formulation techniques such as inclusion complexes and solid dispersions, pharmacologically active compounds or drugs (also referred to as active pharmaceutical ingredients; APIs) are usually not administered to patients on their own as single compounds, but are formulated into carefully designed dosage forms, Pharmaceutical dosage forms provide a platform for repeatable accurate dosing, quality, efficacy, safety, stability as well as high patient acceptance and compliance, dosage forms were made by simply adding pharmacologically inert substances (also referred to as excipients) to the API to make up the required volume of an acceptable dosing unit, selection and production of excipients that fulfil specific functions, beyond just making up volume, such as assisting in production of the dosage form and optimizing drug delivery from novel dosage forms, stability of the API, dose uniformity, effective delivery of the API to the systemic circulation after administration as well as acceptable organoleptic properties, excipients are 90% of the total mass/volume of medicinal products, different classes of pharmaceutical excipients have different requirements in terms of safety evaluation, updates on regulatory requirements for pharmaceutical excipients are continuously introduced worldwide to ensure the safety of patients, multifunctional excipients’ refer to excipients (which can be co-processed for example) that fulfil multiple roles in a dosage form or drug delivery system, for example a direct-compressible filler material that also functions as a binder and/or disintegrant, high functionality excipients’ refers to a single excipient that provides additional functions to innovative drug delivery systems to improve the overall performance of the product with significant economic benefits, high functionality excipient is one that can provide better flow, act as a disintegrant and simultaneously allow a higher drug loading in the dosage form due to its high compressibility, 40% of current medication dispensed to patients in pharmacies exhibit relatively poor aqueous solubility properties, 90% of newly discovered therapeutic compounds in the development phase exhibit poor aqueous solubility, future research regarding the identification of solubility-enhancing excipients is of cardinal importance, functional excipients are needed to assist in overcoming their poor physico-chemical properties, Specialty excipients are used to produce dosage forms that can reduce the number of doses by modifying the rate of drug release or improve drug delivery by targeting drug release in a specific region in the gastrointestinal tract where drug absorption is the highest. Functional excipients are also used to re-formulate existing drugs in order to produce more effective products that are more cost-effective, a drug that exhibits an aqueous solubility lower than 0.1 mg per mL is likely to experience limited bioavailability, and its rate of absorption will be governed by the dissolution rate, Physico-chemical techniques that have been employed to improve the solubility of these drugs include formation of pro-drugs, formation of salts, co-precipitation, solvent evaporation and size reduction (or micronization), Formulation strategies that have been investigated for the same purpose include melt extrusion/granulation, formation of solid dispersions and formation of inclusion complexes. Furthermore, excipients such as surfactants, polymers, super-disintegrants and multifunctional fillers have been included in dosage forms to increase the apparent solubility of drugs, term ‘complex formation’ or ‘complexation’ refers to the binding of two or more individual molecules to form a combined chemical product, which act as a single chemical unit, dosage forms include conventional immediate release tablets, orally disintegrating tablets, effervescent tablets, and modified release dosage forms including slow release or sustained release drug delivery system, excipients that can increase an API’s solubility and dissolution rate include cyclodextrins, disintegrants, pH-adjusting excipients, natural polymers, surfactants, co-surfactants, oils/lipids and sugars, special interest to determine the clinical significance or value of formulation approaches on drug bioavailability and if they could result in decreasing the dose needed to reach effective blood plasma levels, Identifying the correct formulation method and using the suitable excipient in relation to the API may result in efficient pharmacological treatment by means of administrating a lower dose, which may have a significant cost implication.

Author: Mohammad Sadegh Amiri, Vahideh Mohammadzadeh , Mohammad Ehsan Taghavizadeh Yazdi , Mahmood Barani , Abbas Rahdar , and George Z. Kyzas

Gums are carbohydrate biomolecules that have the potential to bind water and form gels regularly linked with proteins and minerals in their construction. Gums have several forms, such as mucilage gums, seed gums, exudate gums, etc. Plant gums are one of the most important gums because of their bioavailability, main feature is high stabilization, viscosity, adhesive property, emulsi?cation action, and surface-active activity, many pharmaceutical formulations use them, plant-based gums and mucilages are the key ingredients due to their bioavailability, widespread accessibility, non-toxicity, and reasonable prices. These compete with many polymeric materials for use as different pharmaceuticals in today’s time and have created a signi?cant achievement from being an excipient to innovative drug carriers. scientists and pharmacy industries around the world have been drawn to uncover the secret potential of plant-based gums and mucilages through a deeper understanding of their physicochemical characteristics and the development of safety pro?le information. This innovative unique class of drug products, useful in advanced drug delivery applications, gene therapy, and biosynthesis, has been developed by modi?cation of plant-based gums and mucilages, Extensive use of various excipients, such as binders, thickening agents, sweeteners, and glidants, which can change the physicochemical properties of the final formulation of the drug and adjust the pharmacodynamic and pharmacokinetic properties, has made significant progress in the field of drug delivery systems, Polymers are used as excipients for the progress of polymer-based drug delivery systems with the purpose of targeted drug delivery , synthetic polymers have high physical, chemical, and mechanical stability but can cause cytotoxicity and are bio-incompatible, synthetic polymers have disadvantages, such as: poor adaptation to the patient’s body, high cost, and can also cause acute and chronic side effects, for example: poly-(methyl methacrylate) (PMMA) can cause skin and eye irritation the utilization of natural polymers has increased, the use of natural plant-derived polysaccharides as excipients has increased in the pharmaceutical industry and can solve formulation problems and reduce the side effects of synthetic polymers, natural polysaccharides are formed by their O-glycosidic linkages by binding monosaccharide residues together and are known as biopolymers, gums and mucilages are among these excipients. They are widely used in the medicine and cosmetic industries and can also be modified for use in a variety of drug delivery systems, these materials can be used in several pharmacological forms, for instance, control release systems, film-coating agents, nanoparticles, viscous liquid formulations such as ophthalmic solutions, suspensions, implants, etc. Gums and mucilages are composed of many compounds, including polysaccharides. The resins and tannins in the gums are responsible for providing and delivering retardant properties to the dosage form and transmitting release inhibitory properties.

Author: Chander Pal Singh Verma, Santosh Verma, Mahendra Singh Ashawat, Vinay Pandit

the ideal characteristic of bioenhancers includes inertness, nontoxic, cost effective and decrease the dose of active constituents. There are lots of natural bioenhancers available such as piperine quercetin, niaziridin, genistein, glycyrrhizin, curcumin, the review focus on plant based bioenhancers and their active principle that produces those effects, there is a need of extensive study on natural bioenhancers which can be utilized in formulation development, Drugs that are administered orally go through a dissolution process and then permeation across the gastric membrane before they can appear in the blood stream, the amount of drug that goes into the bloodstream from its site of administration is defined as its bioavailability, solubility is defined as the property of a substance to dissolve itself into a solid, liquid or a gaseous solvent to form a homogeneous solution of it. Solubility of a drug in gastric media is an essential requirement for an orally administered drug to be absorbed adequately, the majority of factors that affect the bioavailability of a drug other than solubility and permeability include the dissolution rate of the drug, first-pass effect, pre-systemic metabolism of the drug in any other organ and susceptibility to efflux mechanisms, Solubility in the gastric media is a major problem associated with orally administered drugs that leads to erratic bioavailability, use of bio enhancers is a promising approach to overcome the issues related to bioavailability. A bioenhancer enhances the bioavailability of a drug molecule without causing any pharmacological activity of its own, bio enhancers of herbal origin have gained interest recently and many herbal compounds , A herbal bioenhancer is an agent of herbal origin that has the capability to enhance that bioavailability of a drug with which it is combined, without causing any pharmacological activity of its own, Adding a bioenhancer to a drug helps to reduce drug dosage, drug cost, incidences of drug resistance and risks of adverse drug reaction. Most importantly, a bioenhancer improves the efficacy of a drug by enhancing its bioavailability. In addition, adding a bioenhancer also reduces raw material requirement during pharmaceutical manufacturing

Author: Mahendran Sekar, Afikaah Sha An Ali, Ganesh Sundaram Subramanian, Vengata Subramani Manoharan , Isaac Jason J , Phan Ai Yean

Ultrasound is widely used in rehabilitation, primarily for improving connective tissue extensibility and pain relief in musculoskeletal injuries, and for promoting tissue healing and remodeling. Physiotherapists use therapeutic ultrasound more than any other electrophysiological modality, Topical analgesics will activate superficial thermal response receptor, providing hot or cold sensation, topical agents suspended in aqueous gel are more effective in transmitting ultrasound energy, compared to cream-based agents which are less effective, to transmit sound waves, there must be a gel between the ultrasound probe and the skin, Topically applied external analgesics do appear to provide some benefit of pain relief, the active ingredient in most of these is menthol, methyl salicylate, or a combination of the two, menthol is the irritant that do produce a cooling sensation while methyl salicylate do provide a sensation of heat, Aloe vera is one of the plant material known to effectively decrease inflammation and promote wound healing. This brings to a conclusion that Aloe vera was having potential analgesic activity and that can be used in this study.

Author Prasanthi, V. Padmaja, Supriya Chatla

The use of natural products in the prevention and treatment has increased recently, prepare and evaluate the wound healing effect of Terramycin, to screen the wound healing effect of the formulated gel on the animals containing Aloe vera hydro gel and evaluate physical and microbial parameters for the formulated gel, Aloe-vera gel and group II (n=2) rats were treated topically with Aloe vera gel containing antibiotic. In these the Aloe vera containing antibiotic shows activity within 5 days and the aloe vera gel shows activity in 10 days.

Author Habibur Rahman*, Telny Thomas Chungath, Kuppusamy Selvakumaraswamy and Chandrasekar R.

pharmaceutical applications, harried contained in the gel of the leaves. On the other hand, the important pharmaceutical applications such as the use of the dried Aloe vera gel powder as an excipient in sustained release (SR) pharmaceutical dosage, release matrix tablets, dissolution enhancer, Korsemayer Peppas model via anomalous diffusion mechanism, Dissolution kinetics, Sustained release matrix tablets were formulated by direct compression method, Aloe vera polysaccharide as an excipient in formulation research, Formulation development, densities for the powder blend of various formulations, Aloe vera powder improves the solubility without effecting the sustain release pattern, Aloe vera freeze dried powder can be used in the formulation of SR matrix tablets for water insoluble compounds.

Authors: Anja Haasbroek-Pheiffer, Clarissa Willers, Matthew Glyn, Lissinda du Plessis, Josias Hamman

co-administration of absorption enhancing agents with macromolecular drugs (e.g., protein and peptide drugs) has been identi?ed as a means to improve the oral bioavailability of these drugs, Absorption-enhancing agents of natural origins, Aloe vera leaf (e.g., gel and whole leaf extract) have shown a potential to enhance drug permeation across the intestinal epithelial barrier, The mechanism of the drug-absorption-enhancement action and the capacity for absorption-enhancement of the Aloe Vera Gel gel , decrease in transepithelial electrical resistance (TEER) of Caco-2 cell monolayers, indicated the opening of tight junctions between the epithelial cells, transport of Fluorescein isothiocyanate (FITC)-dextran, with a molecular weight of 4 kDa (FD-4), could be enhanced across the Caco-2 cell monolayers, aloe vera gel extract, but not the FITC-dextran with larger molecular weights(i.e., 10, 20, and 40 kDa), which indicated a limited drug absorption enhancement capacity, in terms of the molecular size, paracellular transport of FD-4 occurred after the interaction of the Aloe Vera Gel gel with the epithelial cell monolayers, changes in the F-actin distribution in the cytoskeleton of the Caco-2 cell monolayers was observed by means of a ?uorescence staining, which con?rmed tight junction modulation as the mechanism of action for the absorption enhancement effect of the Aloe vera gel

Author: Himansu Bhusan Samal, Itishree Jogamaya Das, Ch. Niranjan Patra, P. N. Murthy

develop and evaluate dental film containing Aloe Vera extracts for the treatment of Periodontitis, Aloe Vera shows wide spectrum of antibacterial activity against several periodontal pathogen and hence selected for site specific delivery for the treatment of Periodontitis. Aloe vera is formulated into dental films by solvent casting technique using polymers such as Ethyl cellulose, Carbopol 971P and HPMC K4M with PEG 4000 as plasticizer and prepared films (F1-F8) were evaluated for various properties such as weight variation, tensile strength, moisture loss, drug content, in-vitro drug release, In-Vitro dissolution studies showed an initial burst release to achieve immediate therapeutic level of drug in periodontal pocket followed by a progressive fall and extended release of the drug with more uniformity for prolonged period of time. Stability studies did not show any significant changes with respect to content and appearance. In-vitro experiments demonstrated that the prepared film F8 represent a suitable dosage form to release Aloe vera for 96 h and considered as the Optimized formulation, Periodontal disease is recognized as a major public health problem throughout the world and occurs in all groups, ethnicities, races, genders and socioeconomic levels, it is characterized by inflammation and degeneration of the gums, supporting bone, periodontal ligament and cementum and accumulation of bacterial pathogens, mainly within the periodontal pockets, Periodontal disease commonly refers to inflammatory diseases that are plaque induced i.e. gingivitis and periodontitis, Gingivitis, the moderate stage of disease caused by an accumulation of supragingival plaque and characterized by swelling, light bleeding and redness of the marginal gingiva. Gingivitis is associated with a change in the microflora, shifting from a Gram-positive anaerobic flora to a more Gram negative one. Periodontitis, a more severe stage of periodontal disease, results in the resorption of the alveolar bone and detachment of the periodontal ligament supporting tooth. Periodontitis is an inflammatory response to the overgrowth of anaerobic organisms, Aloe-Vera is one such product exhibiting multiple benefits and has gained considerable importance in clinical research. Since Aloe-Vera extracts shows low intrinsic toxicity along with a wide spectrum of biological actions like antimicrobial, anti-inflammatory, antioxidant, astringent, and other useful properties, it is very useful in Dentistry also, the present study was aimed to formulate site-specific controlled release dental devices containing Aloe Vera for the treatment of periodontal diseases and then evaluated for their physicochemical properties including weight variation, thickness, and estimation of drug content, stability, compatibility, In vitro drug release studies and in vitro antibacterial activity.

Authors Divya Bansal/ Bhargava , Manoj Choudhary, Nazneen Dubey, Aditya Ganeshpurkar, Vikas Pandey, Tushar Salukhe

Natural gums and mucilage which hydrates and swells on contact with aqueous media are used as additives in the formulation of hydrophilic drug delivery system, develop a new monolithic matrix system for complete delivery, zero-order manner over an extended time period using processed Aloe vera gel mucilage (PAG) as a release modifier, dry blending of selected ratios of polymer and ingredients using direct compression technique, Physicochemical properties of dried powdered mucilage of Aloe Vera Gel , formulations of pioglitazone HCl and Aloe Vera Gel mucilage, direct compression technique, uniformity of weight and drug content, swelling behavior, Aloe vera mucilage powder can be used as a matrix forming material for controlled release of Pioglitazone HCl matrix tablets, use of natural occurring biocompatible polymeric material for designing of dosage form for oral controlled release administration, Gums and mucilage contain hydrophilic molecule, which can combine with water to form viscous solution or gels, Natural gums and mucilage, which hydrates and swells on contact with aqueous media, additives in formulation of hydrophilic drug delivery system, compliance and flexibility in developing dosage forms, oral drug delivery systems, development of such a system was to make use of Aloe Vera Gel gel as a release retardant material to control the rate of drug release by the tablets, compressibility index values up to 15% result in excellent flow properties, evaluation tests, such as thickness, hardness, friability, and uniformity of drug content, rate of drug release from the tablet formulations aloe vera mucilage powder 200X was highest, Tablets with high concentration of Aloe Vera Gel mucilage exhibited slow release of pioglitazone HCl as compared to commercially available SR tablet, Aloe vera mucilage act as a release retardant

Authors: Anirban Ray, Sampad Ghosh

nutraceutical and cosmeceutical potential of Aloe vera L., human well-being, Polysaccharides are demonstrated as the major component compounds for the bioactivities of Aloe Vera Gel gel, bioactivities, composition, and proportion of gel-components significantly influence the bioactive potential of aloe gel, aloe gel would be of help in optimizing the component of the value chain of aloe processing, bio-active potential to ensure the effective application of Aloe vera gel, biological activity of any substance is mainly implicated by its compositional features, mannose, glucose and galactose monomers which constitute the structural reserve polysaccharide acemannan or ?-(1, 4)-linked acetylated mannose , The structural monsaccharides are present in ?(1,4)- linked mannoses, 1 ?(1,4)-linked glucose, and 1 ?(1-6)-linked galactose form, and some of the mannose monomers are modified by addition of an acetyl group, The molar ratio of sugar and linked acetyl group present in this molecule is 1:3, polysaccharides contain 1?4 glycosidic linkages in between glucose and mannose moiety (glucose: mannose = 1:2.8). Aldopentose, acetylated glucomannan, galactogalacturan, glucogalactomannan, galactoglucoarabinomannan are also the important oligosaccharides or polysaccharides present in Aloe vera, average molecular weight of polysaccharides of the gel was found to be 2 million Da or above and constitutes approximately 0.20% – 0.30% of fresh Aloe gel, polysaccharide molecules can hold water molecules in inter-molecular space and attributes the humectant activity to Aloe Vera Gel, immunomodulatory and functional properties to Aloe Vera Gel, act as biological response modifier, Aloe Vera mainly composed of six different types of compounds namely, poly and mono saccharides (mannose, glucose, glucomannan, acemannan etc.), phenolics, vitamins, enzymes, low molecular weight substances and minerals.

Authors Kiran Sharma, Ashu Mittal, Nitesh Chauhan

Skin penetration enhancers, enhancing drug penetration into the skin through transdermal drug delivery system or topical administration, skin penetration enhancers are molecules which reversibly remove the barrier resistance of the stratum corneum and allow drugs to penetrate more readily to the viable tissues and thus enter the systemic circulation, A. vera gel increased the in vitro skin penetration of compounds depending on their molecular weights, with an apparent inverse correlation between enhancement ratio and molecular weight of the compound, penetration enhancement effect of the aloe gel, pull effect of complexes formed between the compound and the enhancing agent within the aloe gel, administer drugs through skin is transdermal patch, delivery rates tend to be below therapeutic levels due to the barrier function of the skin, Transdermal delivery of drugs , oral or intravenous administration, though human skin, human skin provides an effective barrier to the permeation of most drugs in the form of stratum corneum, drugs must breach this barrier and permeate the skin at a rate sufficient to attain effective plasma concentration, enhance the skin permeation rate of active moieties, use of chemical penetration enhancers such as DMSO, DMF, azone, ionic surfactants, but their use are also associated with unpleasant and toxic side effects, natural compounds as permeation enhancers to improve drug permeation that also exhibit low toxicity while maintaining their enhancing activity, natural absorption promoters documented so far include essential oils, terpenes, terpenoids, fatty acid esters, fatty acid glycols, and herbal extracts, herbal penetration enhancers which have received much attention and an enhancement system based upon a product is ‘Aloe Vera’, which appears as an attractive prospect due to its purported skin friendly and humectant properties, Aloe Vera also possess skin penetrative property, is a good vehicle for transport other substances, aloe Vera is responsible for increased skin penetration of co-formulated drugs, Aloe Vera Gel promotes wound healing by directly stimulating the activity of macrophages and fibroblasts, Fibroblast activation by Aloe Vera Gel has been reported to increase collagen and proteoglycan synthesis, thereby promoting tissue repair, polysaccharides composed of several monosaccharides, predominantly mannose. It has been suggested that mannose 6-phosphate, the principal sugar component of Aloe Vera Gel, may be partly responsible for the wound healing properties of the gel. Mannose 6-phosphate can bind to the growth factor receptors on the surface of the fibroblasts and thereby enhance their activity, mechanism of action of acemannan appears to be twofold. First, acemannan is a potent macrophage-activating agent and therefore may stimulate the release of fibrogenic cytokines. Second, growth factors may directly bind to acemannan, promoting their stability and prolonging their stimulation of granulation tissue, The higher the molecular weight of the co-applied compound, the less of the gel components were transported across the skin, displacement of Aloe vera components from the penetration pathways and thereby it inhibits, permeation of the gel components more effectively than the smaller compounds, intestinal drug absorption enhancement, Aloe Vera has an element called “Lignin” which helps it to penetrate right down to the cellular level, rate of vitamin C absorption- bioavailability of vitamin C was 3 times higher when administered with the aloe gel, For vitamin E, the bioavailability was 3.7 times higher when administered with aloe gel, he mechanism of action of the aloe products to improve the bioavailability of the vitamins was explained to be a possible protection effect against the degradation of the vitamins in the intestinal tract as well as binding of the polysaccharides to the vitamins and thereby slowing down the absorption rate, A. vera gel and whole leaf extract could decrease the transepithelial electrical resistance of intestinal epithelial cell monolayers (Caco-2), thereby indicating opening of the tight junctions between adjacent epithelial cells, aloe vera able to significantly increase the transport of the macromolecular peptide drug, insulin, across the Caco-2 cell monolayers, Drug absorption enhancers are compounds capable of reversibly removing the resistance of the outer layers in the body with minimum tissue damage, thus allowing the drug to enter the blood circulation in sufficient quantities, Drug absorption enhancers are compounds capable of reversibly removing the resistance of the outer layers in the body with minimum tissue damage, thus allowing the drug to enter the blood circulation in sufficient quantities, functional excipients in dosage forms, which include binders, disintegrants, emulsifiers, suspending agents, gelling agents and sustaining agents in modified release tablets, some natural gums and mucilages have been reported to modify the release of drugs from modified release dosage forms such as matrix type tablet, Skin penetration properties: Penetration enhancers work by means of two possible mechanisms: (1) the penetration enhancer increases the solubility of the drug within the SC by altering the partitioning of the drug into the SC and/or (2) the penetration enhancer influences the diffusion of the drug across the SC by disrupting the ordered nature of the skin lipids. Lignins as structural material of cellulose content allows for penetration properties, Aloe Vera can soak into all the layers of the skin and this may be helpful in increasing the penetration of certain drug molecules across the skin, as lignins can penetrate the toughened areas of the skin

Author: Marios Spanakis, Ioannis Vizirianakis, Ioannis Niopas

modulation of P-glycoprotein function by Aloe vera juice in Caco-2 cells, Aloe vera exhibited the capability to inhibit P-gp thus raising the possibility of the emergence of adverse drug reactions (ADRs), P-glycoprotein (P-gp), an ABC-transporter encoded by ABCB1 gene in humans localized in small intestine, is responsible for the active efflux of several xenobiotics including a wide number of drugs influencing their bioavailability, P-gp function is modulated via inhibition or induction which is causally related to several cases of clinically relevant drug-drug, drug-herb and/or drug-food interactions, Caco-2 cells are expressing P-gp protein and represent a well-documented in vitro model for permeability studies, the capacity of commercially available Aloe vera juice (AV) to modulate permeability of the P-gp substrate, Rhodamine-123, (Rho-123) in Caco-2 cells, Rhodamine-123 is been transported from the intracellular, environment exclusively through the efflux function of P-gp, the presence of Aloe vera extracts on Caco-2 cells lead to reduction of both the permeability and the cumulative transport of Rho-123 from basolateral to apical side with a dose dependent manner, Aloe vera extract in concentrations of 0.05 mg/ml and 0.1 mg/ml reduced TEER values of the Caco-2 membrane in a range up to 40% of the initial value upon exposure of cells for 120 min and/or 180min, Besides the decrease of the TEER values, paracellular transport of Rho-123 did not seem to occur (Figures 4 and since TEER values remained over 400?/cm2 during transepithelial experiments, the results presented reveal a capability of Aloe vera extracts to modulate P-gp function in a dose dependent manner by influencing the extend of transport of Rhodamine123 through Caco-2 cell monolayer cultures, further work is needed in order to more thoroughly delineate the effects of Aloe vera on P-gp function and evaluate the clinical relevance of possible interactions with drugs.

Author: Vilas Asaram Arsul, Swaroop R Lahoti

Proper design and formulation of a dosage form requires consideration of the physical, chemical and biologic characteristics of the drug substances and pharmaceutical ingredients to be used in fabricating the product, excipients facilitate the formulation design and perform a wide range of functions to obtain desired properties for the finished drug product. Polysaccharide hydrocolloids including mucilages, gums and glucans are abundant in nature and commonly found in many higher plants, polysaccharide hydrocolloids including mucilages, gums and glucans are abundant in nature and commonly found in many higher plants. These polysaccharides constitute a structurally diverse class of biological macromolecules with a broad range of physicochemical properties which are widely used for various applications in pharmacy and medicine. Polysaccharide (Gums and mucilages) functions as versatile excipients such as Suspending Agent, Emulsifying Agent, Binder, Gelling Agent, Disintegrant etc. for pharmaceutical formulations. The polysaccharides can also be modified in different ways to obtain tailor-made materials for drug delivery systems and thus can compete with the available synthetic excipients, Excipients are the additives used to convert active pharmaceutical ingredients into pharmaceutical dosage, Excipients were defined as ‘the substance used as a medium for giving a medicament, that is to say with simply the functions of an inert support of the active principle or principles, development of the newer excipients, Polysaccharide in Plant Parts, Polysaccharide hydrocolloids including mucilages, gums and glucans are abundant in nature and commonly found in many higher plants. These polysaccharides constitute a structurally diverse class of biological macromolecules with a broad range of physicochemical properties which are widely used for various applications in pharmacy and medicine, Sustained release, Suspending agent, emulsifying agent, gelling agent in suppositories, surgical lubricant, laxative, Gelling agent, sustained release agent, controlled release tablet, stabilizer in emulsions and suspensions, demulcent and laxative, tablet binder, sustaining agent, emollient, Binder, disintegrant, thickening agent, emulsifier, sustained release agent, Cathartic, lubricant, dental adhesive, sustaining agent in tablets, disintegrating agent in tablets, stabilizer in toothpaste and ointment

Author K. Subramanian , S.Narmadha, U.Vishnupriya & V.Vijayakumar

Increasing research interest has been focused on controlled drug delivery through tablet form using synthetic and natural biocompatible polymers as carriers, synthetic polymer drug carriers will be safely metabolized, they will not impart any health benefit unlike the natural carriers such as chitosan, starch , aloe vera, etc, , For the same biofluid, the observed higher drug release rate for paracetamol compared to aspirin was attributed to the difference in their structure and solubility. The enhanced drug dissolution with the increased content of amla juice powder in the tablet was more likely attributed to its highwater solubility, The enhanced drug dissolution with the increased content of amla juice powder in the tablet was more likely attributed to its highwater solubility. Aspirin is released at a faster rate in SGF (pH of 1.2) compared to SIF (pH of 7.2). The order of release rates of aspirin and paracetamol from the respective tablets in SIF is reversed in SGF. Replacing a part of aloe vera gel powder by chitosan, decreased the drug release rate. These observations demonstrated that by fine tuning the tablet compositions with aloe vera gel powder, amla juice powder and chitosan and media pH, desirable controlled drug release characteristics can be achieved Medications is the widely practiced method globally for treating diseases. Rate preprogrammed drug delivery for predetermined duration of medication is increasingly being employed in advanced control release technology. Different types of controlled-release dosage forms have been developed for improved clinical efficacy of drug and patient compliance. Among the dosage forms the tablets have an attractive option for pharmaceutical scientists and clinicians because they offer the advantages of accurate unit-dosing, better patient compliance, ease of large-scale manufacturing, and low production cost. Biodegradable biocompatible polymer and polymer hydrogels are widely employed as drug carriers in tablets. Drug release from hydrophilic matrix tablet is strongly influenced by the proportion and nature of matrix forming polymer apart from the dimensions and geometry of the tablet. It is one of the least complicated and convenient approaches to manufacture sustained release dosage forms that consist of a drug dispersed in a polymer. Since the polymer drug carriers usually do not impart any medical benefit other than controlling the release rate and as a binder matrix, present investigation involves the use of a natural carrier such as aloe vera gel having inherent tremendous medicinal values, It is to be noted that aloe vera gel powder may enhance the intestinal absorption, sustained release of pharmaceutical dosage forms, effective delivery of poorly absorbable drugs, enhancement of bioavailability of vitamin C, protection against degradation of vitamins. When taken internally along with the drug it may improve the digestive Musculo-skeletal and immune-related conditions apart from acting as an antioxidant. Moreover, natural polymers are biocompatible and enhance the drug release efficacy with reduced toxicity, and improved patient compliance with in vivo degradation at a well-defined rate, and can be readily isolated and purified in large quantities, preparation of tablets of non-steroidal drugs like paracetamol and aspirin using Aloe vera gel powder as a carrier in the presence of amla juice powder, chitosan , release profiles of the drugs UV spectrophotometrically in simulated biological fluids for the evaluation of drug release characteristics, Aspirin and paracetamol (non-steroidal drugs) tablets were made using carefully dried aloe vera gel powder as the natural drug carrier along with amla juice powder as nutrient excipient with varying compositions and in vitro release characteristics of these drugs in SIF and SGF at 37o C were evaluated UV spectrophotometrically. The release rates of these drugs were different in both the fluids which are having different ionic strength and pH values. The release rate for paracetamol is greater than that for aspirin in both the fluids which may be attributed to their differences in chemical structure and solubility. The enhanced drug release rate both in SIF and SGF with increasing content of amla juice powder in the tablet for the constant content of the drug may be attributed to the more likely development of porosity in tablets in these fluids due to the high solubility of amla juice powder. Aspirin is released at a faster rate in SGF (pH of 1.2) compared to SIF (pH of 7.2). The order of release rates of aspirin and paracetamol from the respective tablets in SIF is reversed in SGF. Replacing a part of aloe vera gel powder by chitosan, a natural inherently antimicrobial biopolymer decreased the drug release rate. Value of power law exponent “n” greater than 0.5 for the tablets investigated implied that the predominant drug release mechanism is non-Fiskian. The use of aloe vera gel powder a natural polymer as a carrier along with amla juice powder, will impart multiple health benefits and which in turn may minimize the side effect of drugs unlike in the tablets fabricated using synthetic biocompatible polymers as carriers. Hence the present investigations demonstrate that plant derived natural biopolymers with medicinal values may be successfully employed as a drug carrier for controlled and desirable drug delivery applications with additional health benefits associated with the herbal extracts used as carriers and excipient by fine tuning the tablet composition and media ph. The heterogeneous composition of the aloe vera pulp and amla juice may contribute to the diverse pharmacological and therapeutic activities of the tablet.

Author Beneke C., Viljoen A., Hamman J.

Aloe vera , Drug absorption enhancement , Transepithelial electrical resistance, In vitro transport, aloe materials on the transepithelial electrical resistance (TEER) as well as transport of a model compound (atenolol) in the apical-to-basolateral direction across rat intestinal tissue, Aloe vera gel polysaccharides have potential as drug absorption enhancing agents in novel pharmaceutical drug delivery systems, function of epithelial cells is to maintain distinct compartments within the body and also to act as barriers to separate the body from the external environment, molecules can cross the intestinal epithelium by three main pathways, namely transcellular passive diffusion, paracellular passive diffusion and carrier-mediated transport, drugs exhibit poor absorption after oral administration, Poor drug absorption across the intestinal epithelium is in many cases attributed to unfavorable physico-chemical properties of the drug molecule such as hydrophilicity and a large molecular weight, intestinal absorption of these drugs can be increased by different techniques such as co-administration of absorption enhancing agents, absorption enhancing agents may facilitate the absorption of poorly absorbable drugs by different mechanisms such as opening of tight junctions or changing the membrane structure or targeting transporter proteins, damage to the mucosal epithelium is a major problem with drug absorption enhancing agents, drug absorption enhancing agents can increase intestinal drug absorption in a reversible way without causing damage or toxic effects have ignited renewed interest in finding safe and effective drug absorption enhancers to increase drug bioavailability, Tight junctions between epithelial cells are dynamic structures that can be modulated by certain chemicals in such a way to enlarge the pores or fenestrae and thereby allow paracellular passage of hydrophilic macromolecules, drug absorption enhancement has the additional advantage of avoiding enzymatic degradation of susceptible molecules. Compounds that selectively open the intestinal epithelial tight junctions, referred to as paracellular permeability enhancers, have shown potential as novel excipients in advanced drug delivery systems, polysaccharides in Aloe Vera Gel gel consist mainly of linear chains of glucose and mannose molecules with considerably more mannose present than glucose. Acemannan (or aloverose) is a ?-(1,4)-linked galactomannan with acetylated mannose residues, activities of acemannan include antiviral effects, wound healing acceleration, anti-cancer, activation of macrophages and stimulation of T cells, high molecular weight polysaccharide isolated from aloe gel is aloeride. A smaller form of highly acetylated polysaccharide known as modified aloe polysaccharide was isolated from cellulose-treated aloe gel, Aloe Vera Gel gel and whole leaf materials were able to significantly reduce transepithelial electrical resistance (TEER) of Caco-2 cell monolayers and also significantly enhanced the transport of insulin across this cell culture model, transport enhancement effect of Aloe Vera Gel leaf materials is probably due to the opening of tight junctions to allow paracellular transport, TEER is a measure of tight junction integrity between adjacent intestinal epithelial cells, the size of the openings of the tight junctions increases in the presence of a paracellular permeability enhancer, the TEER of the intestinal epithelium will be reduced because of the increasing flow of ions through the opened tight junctions and intercellular spaces , aloe materials investigated in this study lowered the TEER of the excised rat intestinal tissue statistically significantly (P < 0.05) compared to the control group (atenolol alone), polysaccharides in the aloe materials are responsible for or contribute to a large extent to the effect on the TEER, reduction in TEER of the excised rat intestinal tissue by the aloe materials indicates their ability to open the tight junctions between epithelial cells, which indicates the potential of these materials to enhance drug transport across intestinal tissues, high molecular weight polysaccharides such as chitosan and N-trimethyl chitosan chloride

Author: Joana Simõesa, Fernando M. Nunesb, Pedro Dominguesa, Manuel A. Coimbraa, M. Rosário Dominguesa.

Aloe vera acemannan, backbone of ?-(1?4)-linked D-mannose, mannans, acetyl groups, high abundance of acetylated residues, lower branching, shorter chains, and higher acetylation seems to promote the immunostimulatory activity attributed to these polysaccharides.

Author S.Arunkumar and M. Muthuselvam.

Aloe vera phyto chemical compounds and antimicrobial Activity, Tannin, Saponin, Flavonoids and Terpenoids gave positive results and phlobactanins and Steriods and Steriods gave negative results. In the GC-MS analysis, bioactive phytechemical compounds, antimicrobial activity selected human clinical pathogens, Antifungal activity of Aloe vera, Ayurvedic, medicinal active constituents

Author: Sinha, V.R.; Kumria, R.

Polysaccharides are bacterial enzymes have been used extensively in targeting of the drugs. Various polysaccharides have been investigated for colon specific drug delivery, natural polymers exhibit potential for drug delivery as they are comprised of polymers with a wide range of molecular weights resembles in the indigestion in the stomach and the small intestine, a large number of derivatizable groups, moreover, the polysaccharides are inexpensive, naturally occurring, abundantly available and varying chemical compositions, the most favorable property of these materials is their approval as pharmaceutical excipients, here we provide an overview on polysaccharide-based colon specific drug delivery system, drug delivery that involve a general overview of the gastrointestinal tract, the pH of different gastrointestinal regions, digestive enzymes that are secreted in mouth, stomach and intestines, and the microflora that are presented in colon region. Properties, mechanisms, applications, and patents of various polysaccharides that can be used to target the colon, gastrointestinal tract begins in the mouth, then the esophagus and reaches to the stomach, small and large intestine, and finally to the anus. The tube that initiates from the mouth to the anus in which the movement of muscles took place and release of hormones exist and digestion of enzymes took place. The gastrointestinal tract initiates with the mouth and goes through the esophagus, stomach, duodenum, small intestine then moves to the large intestine (colon), rectum and, finally, the anus, which is also known as alimentary canal, digestive tract and, perhaps commonly known as the GI tract. In an adult male human, the Gastrointestinal (GI) tract is 5 meters (20 ft) long, or up to 9 meters (30 ft) without the effect or action of muscle tone, and comprises of the upper and lower GI tracts, with regard to the rectal route, the drugs do not always reach the specific sites of the colonic disease and the sites of colonic absorption. To reach the colon and to be able to specifically deliver and absorbed there, the dosage form must be formulated taking into account the likely obstacles of the gastrointestinal tract. That is, pH, microflora, enzymes, reducing medium and transit time, pH dependent system, formulation which is coated with enteric polymers release the specified drug when pH moves towards alkaline side, Time released system, Based on the conceptual mode of delaying the release of drug after a lag time of 3-5 hours that is equivalent to small intestine transit time, Pressure dependent system, Based on conceptual mode of the strong peristaltic waves that lead to a temporary increase in luminal pressure in the colon, Microbially triggered system Polysaccharides, Drug are released following degradation of the polymer due to the action of colonic bacteri, Osmotic controlled delivery, Based on the utilization of chitosan gelable properties at acid condition to produce osmotic pressure and its colon specific biodegradation to form in-situ delivery pores for drug reléase, Bioadhesive system, Drug coated with bioadhesive polymer they provide adhesive property at colonic mucosa, Micro particulate carrier system, Based on microparticles which absorb through macrophages present in colon and increase resident time of drug, Dosage Form, Matrices, Compression coated/matrix tablet, Beads, Microparticle, Compression coat, Matrix Tablet, Enteric-coated microsphere, Coating with polymers, Coating with pH sensitive polymers, Coating with biodegradable polymers

Authors FIRMANSYAH, Ferdy; VAJRIKA, Silvi Ayu; MUHTADI, Wildan Khairi

Aloe vera is efficacious as an antibacterial activity , treat acne caused by the bacteria Propionibacterium acnes, viscosity, dissolution, diffusion, and bioavailability of the preparation, determine the effect of the combination of Carbopol 940 base and HPMC as a gelling agent on the physical properties and antibacterial activity of aloe vera gel against P. acnes bacteria, tests of adhesion, dispersibility, and viscosity as well as measurement of antibacterial activity by measuring the diameter of the inhibition zone formed on the media, physical properties of the aloe vera gel, adhesive power, viscosity decreased, dispersion power increased, antibacterial activity so that it can treat skin infections, aloe vera flesh was 100% effective against Gram- negative bacteria and 75.3% against isolated Gram-positive bacteria, aloe vera meat inhibited the growth of Propionibacterium acnes by an average of 8.4 mm and could inhibit the growth of Staphylococcus aureus by 18 mm, topical application is gel with various combinations of Carbopol and HPMC bases, hydrogels are very suitable for topical preparations with excess sebaceous gland function, Carbopol are that it is compatible with various active substances, is bioadhesive, has stability, organoleptic characteristics and good patient acceptance, while HPMC is inert , does not cause skin irritation, has good resistance to microbial attack, and provides film strength. which is good when it dries on the skin, combination of Carbopol and HPMC in the gel preparation of aloe vera flesh extract can affect the physical properties of the gel

Author Jani GK, Shah DP, Jain VC.

Natural gums and mucilage have been widely explored as pharmaceutical excipients. The goal of this study was to extract mucilage from the leaves of Aloe barbadensis Miller and to study its functionality as an excipient in pharmaceutical sustained-release tablet formulations, Sustained-release dosage forms are prepared to achieve a desirable and predictable pharmacodynamics response within appropriate pharmacokinetic parameters, improve patient compliance, reduce side effects, and maximize drug efficacy , creating drug-embedded matrix tablets using direct compression of a blend of drug, retardant material, and additives is one of the simplest approaches for a formulation. One of the most used methods of modulating drug release is including polymeric material within a matrix system. Matrix systems are important because of their simplicity, low cost, the small influence of physiological variables on their release behavior, and their suitability for manufacture on modern high-speed equipment, Drug-release retarding polymers are the key performers in matrix systems. Various polymers have been investigated as drug retarding agents, each presenting a different approach to the matrix system. Based on the features of the retarding polymer, matrix systems are usually classified into three main groups: hydrophilic, hydrophobic, and plastic. Hydrophilic polymers are the most suitable for retarding drug release, and there is growing interest in using these polymers in sustained drug delivery, natural gums and mucilage are well known for their medicinal use. They are widely used in the pharmaceutical industry as thickeners, water-retention agents, emulsion stabilizers, gelling agents, suspending agents, binders, film formers, and sustained-release agents, many plants contain mucilage, which provides high concentration of complex polysaccharides. Mucilages are hydrophilic polymers, It also contains aloetic acid, galactouronic acid, glucosamine, monosaccharides, and polysaccharides. It is used to heal wounds, burns, and to treat eczema and disturbed menstruation, Diclofenac sodium is a potent nonsteroidal anti-inflammatory drug that has anti-inflammatory, analgesic, and antipyretic properties. It is used to treat degenerative joint diseases such as rheumatoid arthritis, osteoarthritis, and ankylosing spondilitis. Diclofenac sodium is rapidly dissolved in intestinal fluid and reaches its maximum blood concentration (Cmax) within 30 min. It is metabolized mainly by hepatic hydroxylation and subsequent conjugation (13). In healthy human volunteers, mean plasma clearance of diclofenac sodium was 16 L/h, and the mean elimination half-life of the terminal phase was 1.2–1.8 h to diminish diclofenac sodium gastrointestinal irritation, which is a common problem with all nonsteroidal anti-inflammatory agents, effective enteric-coated dosage forms are used. Food, however, effectively delays the absorption of the drug, which causes a nonreproducible pharmacokinetic profile, and the drug has no immediate therapeutic effect, Aloe barbadensis and to study the various pharmaceutical properties of the mucilage to assess its functionality as an excipient in pharmaceutical sustained-release formulations, Physicochemical and microbial properties of A. barbadensis mucilage powder 200x was studied for percentage yield, chemical test, particle size, weight loss on drying, solubility, viscosity, pH, swelling index, bulk and tapped density, angle of repose, compression properties, and microbial load, Aloe barbadensis Miller powder appears suitable for use as a pharmaceutical excipient in the formulation and manufacture of sustained-release matrix tablets because of its good swelling, good flow, and suitability for direct-compression formulations. From the dissolution study, it was concluded that the aloe vera gel powder can be used as an excipient for sustained-release, modified-release, and fast-release tablets with suitable modifications.

Author: Deepthi V. Tatiraju, Varsha B. Bagade, Priya J.Karambelkar, V. Jadhav, V. Kadam

Bioenhancers are chemical entities which promote and augment the bioavailability of the drugs which are mixed with them and do not exhibit synergistic effect with the drug, need for bioenhancers arises due to drugs which are poorly available, administered for long periods, toxic and expensive, Bioenhancers can be classified based on their natural origin as well as based on the various mechanisms elicited by them when in combination with drugs to improve their bioavailability.

Author: Thu Han Le , Phan Se Yong, Park Hyun , Jin Jung, Seung Hyun Oh

tight junction-modulating effects of processed Aloe vera gel (PAG), comprising 5–400-kD polysaccharides as the main components, oral treatment of 143 mg/kg Polysaccharides Aloe Gel daily for 10 days improves the age-related leaky gut condition in old mice, by reducing their individual urinal lactulose/mannitol (L/M) ratio. In concordance with in vivo experiments, Polysaccharides Aloe Gel treatment at dose 400 ?g/mL accelerated the polarization process of Caco-2 monolayers. The underlying mechanism was attributed to enhancement in the expression of intestinal tight junction-associated scaffold protein zonula occludens (ZO)-1 at the translation level. This was induced by activation of the MAPK/ERK signaling pathway, which inhibits the translation repressor 4E-BP1. In conclusion, we propose that consuming PAG as a complementary food has the potential to benefit high-risk patients, Intestinal tight junctions are complex structures containing various intercellular membrane proteins (such as claudins and occludin) attached to the scaffolding zonula occludens proteins (ZOs), and through them, to the cytoskeleton actin and myosin of intestinal epithelial cells. Together, they form a barrier that dictates the paracellular absorption of electrolytes and macro-molecules, thereby contributing to safeguarding our body against a bacteria-laden intestinal lumen, leaky gut is assumed to originate due to compromised intestinal tight junction integrity, polysaccharides of Aloe vera gel are likely to possess bioactivity to help alleviate the leaky gut condition, Polysaccharides Aloe Gel increases Tight Junction Proteins of Intestinal Epithelial Cells

Author Tanya M. Barnes, Dalibor Mijaljica, Joshua P. Townley, Fabrizio Spada and Ian P. Harrison

Many dermatological conditions, such as eczema and psoriasis, are treated with topical therapeutic products. Instead of applying the active drug directly onto the skin, it is combined with a vehicle to aid in its delivery across the stratum corneum (SC) and into deeper regions of the skin, namely the epidermis and dermis. Absorption into the systemic circulation is minimized. Topical vehicles are also used as cosmetic moisturizers (often termed emollient therapy) to ameliorate dry skin, which is a cornerstone of the management of various dermatological conditions, including xerosis, eczema, psoriasis, and aging. The most common topical vehicles include ointments, creams, gels, and lotions, among others. It is crucial that topical vehicles are chosen based upon the size and properties (wet/dry, mucous/non-mucous, healthy/diseased) of the skin to be treated in order to optimize application and contact of the product with the skin, as this can have profound impacts on potency, efficacy, and patient compliance. This review examines common topical vehicles used for drug delivery and cosmetic moisturizers, including their formulation, advantages and disadvantages, and effects on the skin. ointment, cream, gel, excipient, humectant, emollient, occludent, drug delivery, dermatitis, regulatory, skin is the outermost defensive barrier, which protects the human body from physical, chemical and microbial insults, and prevents the uncontrolled loss of water, the barrier function of the skin resides in the stratum corneum (SC), which is composed of protein enriched corneocyte layers and intercellular membrane lipids, such as ceramides, cholesterol, and free fatty acids, corneocytes are rapidly and continually replaced to maintain skin hydration, flexibility and structural integrity, and repair any skin damage, a dysfunctional skin barrier leads to skin dryness, and may be due to a genetic predisposition [5]; pathological causes such as eczema, psoriasis or xerosis, environmental insults from the sun, wind or air conditioning, frequent exposure to chemicals such as harsh soaps or detergents, medications such as statins, diuretics or retinoids ; and other causes such as aging, dry skin exhibits a defective desquamation process, where corneocytes are shed as visible scales, causing a cosmetically unattractive rough texture and excessive transepidermal water loss (TEWL), dry skin is unable to efficiently bind and hold water, and favors the penetration of irritants, allergens, and microorganisms, provoking discomfort and itchiness, as well as visible irritation or redness, Thus, there is a need to protect both healthy and dry, compromised skin from a plethora of insults, and to preserve or restore its functional and structural integrity, Topical vehicles are used as carrier systems, which aid in the delivery of an active drug (e.g., corticosteroid, calcineurins, vitamin D derivatives, retinoids) across the SC and into deeper regions of the skin, namely the epidermis and dermis, whilst minimizing absorption into the systemic circulation. These formulations are often used to treat dermatological conditions, such as eczema and psoriasis, to restore the skin barrier, however, topical vehicles may also be used on their own as cosmetic moisturizers (often termed emollient therapy) to ameliorate dry skin, including conditions such as eczema and psoriasis where the use of moisturizers has become pivotal as first-line treatment strategies, the most common topical vehicles include ointments, creams, gels, and lotions, among others. Topical vehicles are chosen based upon the nature (wet/dry, mucous/non-mucous, healthy/diseased) and size of the skin area to be treated to optimize application and contact of the product with the skin, Topical Drug Delivery, Transepidermal Route, Transappendageal Route, The Role of the Vehicle, Delivering drug molecules to and through the skin involves the complex interplay between the active drug, the type of topical carrier system or ‘vehicle’, the choice of excipients, skin type and location, and skin condition. The topical carrier system, or ‘vehicle’, is defined as the substance that carries the chosen active drug into contact with and through the skin at an appropriate level to provide a therapeutic effect, the challenge to topical drug delivery is the transport across the SC. To overcome this barrier, a vehicle must: maintain the solubility and stability of the active drug; release the active drug, depositing it on the skin with even distribution; enable penetration into and permeation through the SC skin barrier; facilitate partitioning from the SC into and diffusion through the viable epidermis; sustain the active drug at the target site for a sufficient duration to provide a therapeutic effect; and limit systemic absorption, furthermore, a vehicle should be soothing and comfortable, spread easily and be aesthetically pleasant, which aids in patient compliance, these important attributes of a topical vehicle are dependent on the selection of the right excipients, topical vehicles can be classified based on their physical state, including semisolids (e.g., ointments, creams, gels) and liquids (e.g., lotions, solutions, foams, sprays) , lotions, gels and solutions are monophasic, ointments and creams are biphasic, whilst foams are triphasic

bioactives are dominated by acemannan, a type of carbohydrate, and related complexes of saccharides, proteins, and lipids, management of cutaneous and some systemic conditions, such as some forms of immune dysfunction, atherogenesis, malignancy, and numerous cell functions, bioactive glycan components, diverse functional roles of glycans, moisturizing cosmetics and soothing topicals, skin products, including lotions and sun blocks, glycobiology, polymannan polysaccharides of Aloe, Intrinsic to glycobiology is glycosylation, This process is the most common form of protein and lipid modification, where saccharides are attached to proteins and lipids through a complex, but ordered, process in the ribosome, endoplasmic reticulum, and Golgi bodies of the cell to enable intracellular functioning and cell-to-cell communication, that glycoconjugates, glycolipids, glycoproteins, and proteoglycans, are critical components of the cell surface recognition process throughout all organ systems, structural diversity, glycans have the capacity to far exceed proteins and nucleic acids. Their structural diversity allows them to encode information for specific molecular recognition and to serve as determinants of protein folding, stability, and pharmacokinetics, glycosylation is one of the most common forms of posttranslational modification, glycobiology and glycosylation; the attachment of saccharide units to proteins and lipids, complex carbohydrates in cellular compartments, extracellular spaces, and body fluids, oligosaccharides, physical protection and tissue elasticity, lubrication, physical expulsion of pathogens, diffusion barriers, protection from proteases, cell migration and wound healing, modulation of membrane receptor signaling, depot (hydrophilic) functions, protection from immune recognition, epigenetic histone modifications, prebiotic support, antigen recognition, uptake and processing, and intercellular signaling.

Authors Carien E. Beneke, Alvaro M. Viljoen and Josias H. Hamman

Drug dosage forms contain many components in addition to the active pharmaceutical ingredient(s) to assist in the manufacturing process as well as to optimize drug delivery, Due to advances in drug delivery technology, excipients are currently included in novel dosage forms to fulfil specific functions and in some cases they directly or indirectly influence the extent and/or rate of drug release and absorption. Since plant polysaccharides comply with many requirements expected of pharmaceutical excipients such as non-toxicity, stability, availability and renewability they are extensively investigated for use in the development of solid oral dosage forms, polysaccharides with varying physicochemical properties can be extracted from plants at relatively low cost and can be chemically modified to suit specific needs. As an example, many polysaccharide-rich plant materials are successfully used as matrix formers in modified release dosage forms. Some natural polysaccharides have even shown environmental-responsive gelation characteristics with the potential to control drug release according to specific therapeutic needs, Polymers have been successfully employed in the formulation of solid, liquid and semi-solid dosage forms and are specifically useful in the design of modified release drug delivery systems, excipients were included in drug formulations as inert vehicles that provided the necessary weight, consistency and volume for the correct administration of the active ingredient, but in modern pharmaceutical dosage forms they often fulfil multi-functional roles such as improvement of the stability, release and bioavailability of the active ingredient, enhancement of patient acceptability and performance of technological functions that ensure ease of manufacture, specific application of plant-derived polymers in pharmaceutical formulations include their use in the manufacture of solid monolithic matrix systems, implants, films, beads, microparticles, nanoparticles, inhalable and injectable systems as well as viscous liquid formulations, within these dosage forms, polymeric materials have fulfilled different roles such as binders, matrix formers or drug release modifiers, film coating formers, thickeners or viscosity enhancers, stabilizers, disintegrants, solubilizes, emulsifiers, suspending agents, gelling agents and bioadhesives, Polymers are often utilized in the design of novel drug delivery systems such as those that target delivery of the drug to a specific region in the gastrointestinal tract or in response to external stimuli to release the drug. This can be done via different mechanisms including coating of tablets with polymers having pH dependent solubilities or incorporating non-digestible polymers that are degraded by bacterial enzymes in the colon. Non-starch, linear polysaccharides are resistant to the digestive action of the gastrointestinal enzymes and retain their integrity in the upper gastrointestinal tract. Matrices manufactured from these polysaccharides therefore remain intact in the stomach and the small intestine, but once they reach the colon they are degraded by the bacterial polysaccharides. This property makes these polysaccharides exceptionally suitable for the formulation of colon-targeted drug delivery systems, use of plant-derived polymers and their semi-synthetic derivatives as excipients in the formulation of drug delivery systems. Specific reference is made to the use of natural polymers in the design of novel dosage forms such as modified release matrix type tablets and other new drug delivery systems

Author Lizelle T. Fox, Minja Gerber, Josias H. Hamman

transdermal route of administration offers an alternative pathway for systemic drug delivery with numerous advantages over conventional routes. Regrettably, the stratum corneum forms a formidable barrier that hinders the percutaneous penetration of most drugs, offering an important protection mechanism to the organism against entrance of possible dangerous exogenous molecules. Different types of penetration enhancers have shown the potential to reversibly overcome this barrier to provide effective delivery of drugs across the skin, physical skin penetration enhancers are already employed by the pharmaceutical industry, skin penetration enhancers are associated with irritating and toxic effects. This emphasizes the need for the discovery of new, safe and effective skin penetration enhancers. Penetration enhancers from natural origin have become popular as they offer several benefits over their synthetic counterparts, The skin, as the largest organ of the body, serves as a protective layer of the underlying tissues such as muscles, ligaments and internal organs, shielding it from exogenous molecules as well as from mechanical and radiation-induced injuries. The skin also plays a role in immunology and metabolism, regulates body temperature, serves as an excretory organ through sebaceous and sweat glands and contains sensory nerve endings for the perception of touch, temperature, pain and pressure. The skin varies in color, thickness and presence of nails, hairs and glands between the different regions of the body, although all types of skin have the same basic structure, The external surface of the skin is called the epidermis and consists of keratinized squamous epithelium. The next layer is the highly vascular dermis that nourishes and supports the epidermis and consists of a thick layer of dense, fibroelastic connective tissue which contains many sensory receptors. Underlying the dermis is the subcutaneous layer (or hypodermis) comprising of variable amounts of adipose tissue, the skin has been investigated as a route to deliver drugs topically, regionally or systemically, but unfortunately dermal and transdermal drug delivery is often limited by poor drug permeability , this low permeability can be mainly attributed to the most outer layer of the skin, called the stratum corneum, which serves as a rate-limiting lipophilic barrier against the uptake of chemical and biological toxins and the loss of water, epidermal cell membranes are so tightly joined that there is hardly any intercellular space through which polar non-electrolyte molecules and ions can diffuse [8]. The proteins and lipids of the stratum corneum form a complex interlocking structure, resembling bricks and lipid mortar, the major lipids found in the stratum corneum include cholesterol and fatty acids, Ceramides, in particular ceramide 2 and ceramide 5, play an important role in the stratum corneum’s overall lipid matrix organization and skin barrier function, the ceramides are tightly packed in lipid layers due to the strong hydrogen bonding between opposing amide headgroups. This indicates a transverse organization in addition to the lateral orthorhombic chain organization of ceramide molecules, this hydrogen bonding is responsible for the strength, integrity and barrier properties of the lipid layers in the stratum corneum, the different routes by which a molecule can cross the stratum corneum include the transcellular, intercellular and appendageal (i.e., through the eccrine/sweat glands or hair follicles) routes, the latter route is, however, considered to be insignificant partially due to the appendages occupying only a relatively low surface area corneum’s overall lipid matrix organization and skin barrier function , the ceramides are tightly packed in lipid layers due to the strong hydrogen bonding between opposing amide headgroups., this indicates a transverse organization in addition to the lateral orthorhombic chain organization of ceramide molecules. hydrogen bonding is responsible for the strength, integrity and barrier properties of the lipid layers in the stratum corneum, the different routes by which a molecule can cross the stratum corneum include the transcellular, intercellular and appendageal (i.e., through the eccrine/sweat glands or hair follicles) routes , The latter route is, however, considered to be insignificant partially due to the appendages occupying only a relatively low surface area This causes the range of potential drugs that can be administered transdermal to be very small, which highlights the need for incorporation of penetration enhancers into formulations that could assist in the effective delivery of a larger variety of drugs [5]. Both chemical and/or physical approaches can be used to enhance the penetration of drug molecules across the skin, the properties of an ideal skin penetration enhancer include the following: (1) it should be odorless and colorless; (2) it should be specific in its mode of action; (3) it should be pharmacologically inert; (4) it should be compatible with drugs and other excipients; (5) it should be chemically and physically stable; (6) it should be non-allergenic, non-irritant and non-toxic; (7) its action should be reversible and (8) it should give a rapid effect for a predictable duration of time, the site of action of the chemical skin penetration enhancers is located in the stratum corneum, chemical enhancers can be divided into two broad categories: Those that change partitioning into the stratum corneum and those that influence diffusion across the stratum corneum skin penetration enhancers may act by one or more of three potential mechanisms according to the lipid-protein-partitioning theory. Firstly, penetration enhancers can alter the intercellular lipid structure between the corneocytes to increase diffusivity. Secondly, they can modify intracellular protein domains within the horny layer. Thirdly, they may increase the partitioning of the drug into the skin tissue penetration enhancers of natural origin with reference to their proposed mechanisms of action, effectiveness to deliver drugs across the skin and their shortcomings. The categories of natural skin penetration enhancers that are discussed include essential oils, isolated terpenes (from essential oils), fixed oils (or fatty acids) and complex polysaccharides, Aloe vera Gel/Juice, Polysaccharides and lectins present in the inner pulp or gel of the leaves are considered to be the most important components, in vitro studies showed that Aloe Vera Gel has drug permeation enhancement properties across the skin. Physiochemical properties such as the calculated octanol-water partition coefficient/drug lipophilicity and molecular weight of the model drug compounds were investigated, and they were found to influence the enhancement properties of the Aloe Vera Gel material. In addition, it was found that a significant proportion of Aloe Vera Gel constituents permeated the skin together with the model drug compound Aloe Vera Gel had a higher permeation enhancement effect on drugs with a higher molecular weight. This was explained by the fact that a drug with a larger molecular weight effectively blocks the permeation routes allowing increased possibility for the drug to interact with the enhancing factor and complex with it prior to being transported across the skin. It was further found that “double strength” Aloe Vera Gel at a concentration of 3% (w/v) enhanced the permeation of quinine significantly higher when compared to the “standard” strength, Aloe Vera Gel phytochemicals can be used ‘within-vehicle’.

Author: Chen, W.

Aloe vera (L.) Burm. f. – Asphodelaceae – gel – whole leaf extract – absorption enhancement – Caco?2, confocal laser scanning microscopy, F-actin, FITC-dextran, tight junctions, transepithelial electrical resistance, co-administration of absorption enhancers,

Author: Sam Maher, David J. Brayden, Luca Casettari, and Lisbeth Illum

application of permeation enhancers (PEs) to improve transport of poorly absorbed active pharmaceutical ingredients across the intestinal epithelium is a widely tested approach, permeation enhancers represent a key constituent of conventional oral formulations, permeation enhancer, oral delivery, formulation, permeability, safety, simulated intestinal fluid, hydrophobization, epithelium, a paucity of delivery technologies that address low intestinal epithelial permeability for macromolecules has left pharmaceutical manufacturers with little option but to limit screening of these complex hydrophilic macromolecules or default to parenteral formulation, medicinal chemists in the discovery field should solely focus on safety and efficacy of the active, and rely on formulation and delivery scientists to address sub-optimal solubility, ADME (absorption, distribution, metabolism and excretion), and stability characteristics—or whether medicinal chemists should focus on all of the aforementioned properties to rely less on delivery and formulation scientists, optimizing the molecule and the formulation, improve intestinal permeability in humans, inclusion of an excipient that facilitates transport across the intestinal epithelial barrier, proprietary formulations that attempt to improve oral absorption of macromolecules in humans usually include permeation enhancers (PEs), permeability in oral, nasal, buccal, pulmonary, vaginal, and corneal delivery models. These compounds are broadly categorized as paracellular or transcellular Pes, Transcellular PEs alter epithelial permeability by two contrasting mechanisms, (i) reversible perturbation of the epithelial plasma membrane [9], or (ii) physical interaction with the active to improve passive transcellular permeation (e.g., hydrophobization , surfactant-based PEs are a widely tested category that alter membrane integrity, integrated approach to enabling oral peptide delivery, combining structural engineering and formulation optimization

Author: Chang Liu, Yan Cui, Fuwei Pi, Yuliang Cheng, Yahui Guo, and He Qian

Acemannan, considered one of the main bioactive polysaccharides of Aloe vera, immunoregulation, anti-cancer, anti-oxidation, wound healing and bone proliferation promotion, neuroprotection, and intestinal health promotion activities, biological activities of acemannan, structure-activity relationships of acemannan and its medical applications, pharmacological applications of acemannan, carbohydrate with high molecular weight, bioactive molecule, healthcare products and medicines because of their notable and excellent bioactivities, such as antimicrobial, antitumor, antiviral , and antioxidant activities . In addition, polysaccharides are among the natural biopolymers found on Earth, which are widely used as biomaterials for wound healing, drug delivery and tissue engineering. Aloe vera is one of the few natural plants that are very abundant in polysaccharides, acemannan in medical research, Gel and skin of aloe are the main sources of acemannan, acylation, kind of storage polysaccharide, glucomannan, Acemannan is more abundant in three years old Aloe vera plants, immunomodulatory activity of acemannan on splenic lymphocyte, macrophage and dendritic cells. Acemannan is an important immunoenhancer, can enhance the lymphocyte response to alloantigen, spleen, which combines the adaptive immune system and the innate immune system, is the largest secondary immune organ of the body, Acemannan from Aloe vera can activate effectively regulate immunity, acemannan has a greater stimulatory activity for white blood cell (WBC) counts and spleen cellularity as well as on the absolute numbers of lymphocytes, neutrophils, monocytes in irradiation?induced myelosuppression mice, mitogenic activities of splenocytes were obviously increased as splenic lymphocytes from spleen of Swiss albino mice were cultivated with the acemannan

Author: Roman V. Moiseev, Peter W. J. Morrison, Fraser Steele, and Vitaliy V. Khutoryanskiy

development of advanced ocular formulations an important topic in pharmaceutical science, one of the ways to improve drug delivery to the eye is the use of penetration enhancers, these are defined as compounds capable of enhancing drug permeability across ocular membranes, overview of anatomical and physiological features of the eye and discusses some common ophthalmological conditions and permeability of ocular membranes use of penetration-enhancing compounds (cyclodextrins, chelating agents, crown ethers, bile acids and bile salts, cell-penetrating peptides, and other amphiphilic compounds) in ocular drug delivery, describing their properties and modes of action, ocular drug delivery, cornea, penetration enhancers, ocular conditions, ophthalmology, preferred method of ocular drug delivery is via topical application due to ease of access to the eye and the non-invasive nature of this administration route, Ocular drug penetration is possible via the transcellular pathway, i.e., into and through cells, or the paracellular route, i.e., between cells, or a combination of both pathways, Drug penetration enhancement can be achieved by inclusion of agents capable of modifying the tear film, mucous layer, and ocular membranes in a drug formulation, penetration enhancers are compounds that are able to enhance drug delivery across otherwise impermeable or limited permeability membranes such as the cornea, acting predominantly on the epithelia, penetration enhancers in ocular drug delivery facilitate delivery of active pharmaceutical ingredients through three main mechanisms or their combination Altering tear film stability and the mucous layer at the ocular surface, Modifying membrane components such as lipid bilayers of associated epithelial cells ,Loosening epithelial tight junctions, Penetration-enhancing excipients for use in ocular formulations should ideally have the following characteristics: they should be non-toxic and non-irritating, efficacious at low concentrations, fast-acting, and their effect should be reversible topical drug application is the most widely used treatment in ophthalmology due to its simplicity. However, some obstacles including low permeability of the cornea, tear reflex, blinking, and nasolacrimal drainage hamper drug delivery in this way. The analysis of physicochemical properties of various chemical compounds that cross ocular membranes, coupled with the histological structure of cornea, sclera, and conjunctiva, could be key in understanding the opportunities and obstacles in the ocular drug delivery. Penetration enhancers facilitate delivery of active pharmaceutical compounds through three main mechanisms or their combination: altering tear film stability and the mucous layer at the ocular surface, modifying membrane components such as lipid bilayers of associated epithelial cells, and loosening epithelial tight junctions.

Aisha Saleem, Irum Naureen, Muhammad Naeem, Hafiza Safoora Murad, Samra Maqsood, Gulnaz Tasleem

Digestive Diseases Protection, Aloe vera extract (50%) increased cell viability of dental pulp stem cells being useful for avulsed broken teeth. This effect is attributed to polysaccharides, mainly acemannan, by inducing osteogenic-specific gene expressions, DNA synthesis, growth factor, and JAK-STAT pathway. Moreover, Aloe vera (225 mg/kg) exerted a radioprotective effect against salivary gland dysfunction in a rat model as evidenced in an increase of salivary flow rate, Periodontitis is a serious and common dental affliction in which gums are infected and become inflamed, causing tissue and bone destruction. Gingivitis is the initial phase of periodontitis and is caused by dental plaque. Significant clinical evidence has demonstrated that Aloe vera mouthwash and gel are effective in the prevention and treatment of gingivitis and periodontitis by reducing gingival index, plaque index, and probing depth and by increasing bone fill and regeneration , Aloe vera has proven to be as effective as other usual treatments such as chlorhexidine, alendronate, and chlorine dioxide, Aloe vera gel significantly reduced swelling and postoperative pain, Aloe vera gel and mineral trioxide aggregate as pulpotomy agents in primary molar teeth. The overall success rates at 3, 6, 9, and 12 months was high for patients treated with mineral trioxide aggregate, Aloe vera mouthwash alleviated radiation-induced mucositis severity in patients with head and neck cancers similarly to the reference benzydamine mouthwash, moreover, Aloe vera mouthwash has also demonstrated to be efficient in the treatment of stomatitis (mean intensity and pain) associated with radiotherapy in patients with acute myeloid leukemia and acute lymphocytic leukemia, Aloe vera (systemic as juice and topical as gel) in the treatment of oral submucous fibrosis. Clinical evidence demonstrated that Aloe vera reduced burning sensation and increased cheek flexibility, mouth opening, and tongue protrusion similar to the reference treatment hydrocortisone, hyaluronidase, and antioxidant supplements. In another study on oral submucous fibrosis, the combination of Aloe vera gel with physiotherapy was more efficient in decreasing burning sensation and increasing tongue protrusion, mouth opening, and cheek flexibility than the combination of antioxidant capsules with physiotherapy, gastroesophageal reflux disease is a common chronic digestive disease in which gastric acids move up into the esophagus. Aloe vera syrup (10 mL/day) for 4 weeks reduced the frequency of symptoms of gastroesophageal reflux diseases including heartburn, food regurgitation, dysphagia, flatulence, belching, nausea, and acid regurgitation without causing adverse effects (only one case of vertigo and another of stomach ache were reported), gastritis is an inflammation of mucous membrane layer of the stomach. Aloe vera gel protected in a Balb/c mouse model of alcohol-induced acute gastritis by increasing matrix metalloproteinase-9 inhibitory activity , the topical administration of Aloe vera 3% ointment alleviated the symptoms of diarrhea and fecal urgency in patients with acute radiation proctitis induced by radiotherapy of the pelvic area, Moreover, Aloe barbadensis extract (Innovaloe aloe vera gel powder 200X) reduced, but not significantly, the severity of gastrointestinal symptoms in patients with irritable bowel syndrome compared to a control group, revealed that Aloe polysaccharide (15 mg/kg) protected rats from 2,4,6-three nitrobenzene sulfonic acid colitis induced by increasing JAK2, p-JAK2, STAT-3, and p-STAT3 protein expression. Furthermore, Aloe vera cream applied three times daily for 6 weeks reduced chronic anal fissure pain and hemorrhaging after defection and promoted wound healing in a prospective double blind clinical trial, skin protection study the ability of Aloe vera and active compounds in wound healing. The immortalized human keratinocyte HaCaT cell line, the primary normal human epidermal keratinocytes HEKa cell line, and fibroblasts cell lines, Aloe vera up-regulated TFG?1, bFGF, and Vegf-A expression in fibroblasts and increased keratinocyte proliferation and differentiation by lysosomal membrane stability [28,29,30,31,32]. Moreover, Aloe vera solution could accelerate corneal wound closure at low concentrations (?175 ?g/mL) by increasing type IV collagen-degrading activity in a cellular model of primary cultures of corneal epithelial cells, aloe polysaccharide (20, 40, and 80 µg/mL for 24 h) could be a beneficial agent in psoriasis as evidenced in the inhibition of TNF-? levels and IL-8 and IL-12 protein expression in human keratinocyte HaCaT cell line, Application of topical Aloe vera favored wound healing in animal models with dermal incisions by reducing inflammatory cell infiltration, increasing CD4+/CD8+ ratio lymphocytes, and improving epidermal thickness and collagen deposition, in another study conducted in Indonesia with several medicinal plants, the effect of Nigella sativa oil gel and Aloe vera gel to treat diabetic ulcers was investigated. Aloe vera resulted to be more efficient in improving wound healing on alloxan-induced diabetes in Wistar rats with wounds on dorsum as evidenced by a decrease of necrotic tissue and inflammation and an improvement of re-epithelialization, furthermore, a UV-induced mice model revealed that Aloe vera gel powder increased epidermal growth factor and hyaluronan synthase and reduced matrix metalloproteinases expression (types 2, 9, and 13) , aloe sterols are involved in this UV protection, likewise, it has been observed that Aloe vera protected against X-radiation through antioxidant mechanisms (increased antioxidant enzyme activity and GSH content and reduced ROS production and lipid peroxidation), effectiveness of Aloe vera on ulcers. Hence, the administration of Aloe vera gel twice daily for 3 months improved and accelerated wound healing as well as reduced hospitalization time [, moreover, in a randomized, triple-blind clinical trial with 80 patients hospitalized in the orthopedic ward, demonstrated that Aloe vera gel twice daily for 10 days prevented the development of pressure ulcers on the areas of hip, sacrum, and heel. Moreover, clinical trials have demonstrated that Aloe vera facilitated rapid tissue epithelialization and granulation in burns, promoted healing of cesarean wound, and accelerated wound healing of split-thickness skin graft donor sites , Furthermore, Aloe vera has been investigated in randomized, double-blind, placebo-controlled studies for its benefits to maintain healthy skin. Therefore, the daily oral intake of 40 µg of Aloe sterol (cycloartenol and lophenol) for at least 12 weeks improved skin elasticity in men under 46 years exposed to the sunlight but do not use sunscreen to protect themselves, reduced facial wrinkles in Japanese women over 40 years old by stimulating hyaluronic acid and collagen production, and increased gross elasticity, net elasticity, and biological elasticity in women aged 30–59 , however, despite clinical evidence on the protective role of Aloe vera in the skin, there are clinical trials that have not yet found effectiveness of this medicinal plant, particularly in decreasing radiation-induced skin injury. Two clinical trials have been published between 2014 and 2019 in relation to this effect. Both studies found that topical administration of Aloe vera as gel or cream did not reduce the prevalence and severity of radiotherapy-induced dermatitis and skin toxicity in breast cancer patients compared to control group, acemannan increased IL-6 and IL-8 expression and NF-?B/DNA binding in human gingival fibroblast via a toll-like receptor signaling pathway. Since there is a relation between high IL-1? levels and periodontal diseases, Aloe vera 200x, a standardized Aloe vera extract which contains alin and acemannan on the activation, proliferation, and cytokine secretion of human blood T cells obtained from healthy individuals aged 18–60, and they found that it decreased CD25 and CD3 expression on CD3(+) T cells. Moreover, Aloe vera 200 x exhibited concentration-dependent T cell proliferation suppression and IL-2, IFN-?, and IL-17A reduction. Moreover, the anti-inflammatory effect of Aloe vera has also been investigated in an acetaminophen-induced hepatitis (inflammatory condition of the liver) mice model. The results of this study revealed that Aloe vera (150 mg/kg) reduced hepatic MDA, IL-12, and IL-18 levels and ALT and increased GSH content, Antioxidants are compounds that prevent or slow down biomolecule oxidative damage caused by ROS through free radical scavenging, metal chelation, and enzyme regulation, antioxidant activity is related to a high content in alkaloids, glycosides, phenolic compounds, flavonoids, and saponin glycosides. Moreover, Aloe vera ethanol extract protected, particularly human microvascular endothelial cells, against hydrogen peroxide and 4-hydroxynonenal-induced toxicity by reducing ROS production and HNE-protein adducts formation, the antioxidant activity of Aloe vera and related compounds (10 µM) which possess peroxyl radical scavenging activity and reducing capacity, part from these in vitro assays, in a clinical trial with 53 healthy volunteers, the intake of Aloe vera gel extract (14 days) increased total antioxidant capacity of plasma of subjects, antimicrobial activity of Aloe vera and its main constituents. Most of these studies are in vitro and focus on the antibacterial activity. One of the most studied bacteria are Staphlococcus aureus and Pseudomonas aeruginosa. Hence, Aloe vera aqueous extract reduced growth and biofilm formation against methicillin resistant Staphylococcus aureus, moreover, this bacteria has also been inhibited by Aloe vera gel (50% and 100% concentrations), along with other oral pathogens obtained from patients with periapical and periodontal abscess including Actinobacillus actinomycetemcomitans, Clostridium bacilli, and Streptococcus mutans using disc diffusion, micro-dilution, and agar dilution methods, one of the compounds attributed to antibacterial activity against Staphylococcus aureus is aloe-emodin which acts by inhibiting biofilm development and extracellular protein production , in the case of Pseudomonas aeruginosa, Aloe vera extracts have shown to inhibit the growth of multidrug-resistant Pseudomonas aeruginosa isolated from burned patients with wounds infections at MIC50 and MIC90 values of 200?µg/mL, pseudomonas aeruginosa growth and biofilm formation inhibition has been also demonstrated for Aloe vera inner gel, this Aloe vera inner gel also inhibited other Gram-negative bacteria (Helicobacter pylori and Escherichia coli) as well as the fungus Candida albicans, moreover, in another study, Aloe vera hydroalcoholic extract showed antibacterial activity against Enterococcus faecalis, an infecting microorganism of the root canals of teeth, with inhibition zones of 13 mm (saturated) and 9.6 mm (diluted) , furthermore, concentrations up to 1 mg/mL of Aloe vera aqueous extracts could inhibit Mycobacterium tuberculosis growth, which is the pathogen Molecules

Author: Nikolai Petrovsky and Peter D Cooper

protective immune response, sufficient strength and duration to prevent or attenuate the virulence of pathogenic organisms, systemic delivery of immunologically active contaminants, immunogenicity, an adjuvant is defined as any compound that enhances the immune response, to enhance immunogenicity, provide antigen-dose sparing, to accelerate the immune response, reduce the need for booster immunizations, increase the duration of protection, or improve efficacy in poor responder, compound that enhance with maximum tolerability and safety, carbohydrate-based compounds have many favorable properties

Author: Ranade AN, Wankhede SS, Ranpise NS, Mundada MS.

Usual treatment for Helicobacter pylori-induced peptic ulcer includes a ‘triple therapy’ consisting of two antibiotics (amoxicillin and clarithromycin) and a proton pump inhibitor (omeprazole), retain the drug in stomach for better antiulcer activity and substituting one of the synthetic drugs in this therapy with a herbal alternative. Hence, aim of the present work was to design and develop a bilayer floating tablet of amoxicillin and Aloe vera gel powder for the treatment of peptic ulcer. A. vera gel powder is used for its cytoprotective action. Bilayer floating tablets were prepared by applying direct compression technique. The proportion of sodium bicarbonate and citric acid was adjusted to get the least possible lag time with good matrix integrity and total floating time. Polymer concentration was adjusted to get the maximum release in 8 h. The formulation was developed using hydroxypropyl methyl cellulose (HPMC) K4M and HPMC K100M in a ratio of 85:15 along with 1:4 ratio of effervescent agents was found to give floating lag time of less than 1 min with total floating time of more than 8 h and 97.0% drug release in 8 h. In vivo study in rats meets the requirement of antiulcer activity for bilayer tablet in comparison to single amoxicillin as standard, Helicobacter pylori infection need eradication therapy with antimicrobial agents in addition to anti-secretory drugs. Triple therapy includes proton pump inhibitor bid, amoxicillin 1 g bid and clarithromycin 500 mg bid, is made of combining amoxicillin and Aloe vera gel powder in the form of a bilayer tablet; which can work as an alternative to triple therapy where proton pump inhibitor is replaced by a herbal component which can help in showing better response of amoxicillin against H. pylori by acting as a cytoprotective agent. Reduction in the number of synthetic drug molecules in the therapy can reduce the chances of side effects associated with synthetic drug molecules, Amoxicillin (?-aminohydroxybenzylpenicillin) is a semisynthetic antibiotic, belonging to the ?-lactam family (penicillin). Elevation of beta-lactam concentration demonstrates increased bacterial killing, only until a finite point which tends to be about four times the minimal inhibitory concentration. Further elevation is not associated with increased bactericidal potency, the physicochemical properties of mucus vary considerably at different pH values and acid inhibition (for example by omeprazole) may increase the permeability of mucus to antibiotics, however, long-term monotherapy of gastric ulcer patients with amoxicillin is ineffective even at high daily doses, apparently due to limited contact time with the target site when administered in a conventional oral dosage form, Aloe vera gel exhibited concentration-dependent inhibition of gastric acid secretions by direct interaction with the acid-producing cells or possible interaction with H2 receptors on the parietal cells. A. vera gel has been demonstrated to protect human beings and rats against gastric ulceration. This antiulcer activity is due to its anti-inflammatory, cytoprotective, healing and mucus stimulatory effects, Aloe vera has gastroprotective activity at lower concentrations due to the presence of lectins. Lectins are proteins/glycoproteins which can recognize and binding to carbohydrate moieties. It has been shown that lectins inhibit aminopyrine uptake by parietal cells, ability of gel powder to inhibit gastric acid output maybe as a result of direct action on the acid-producing cells, Retention of amoxicillin and Aloe vera gel in the stomach would result in better action against peptic ulcer by maintaining the effective drug concentration. Thus, the objective of the present investigation involves development and evaluation of a bilayer gastro-retentive floating tablet of amoxicillin and Aloe vera gel powder for treatment of peptic ulcers. Here, amoxicillin will be systemically absorbed, and Aloe vera gel powder will show local effect.

Author Maharjan H. Radha and Nampoothiri P. Laxmipriya?

Aloe vera, medicinal properties, Immunomodulatory effect, own regulates lipopolysaccharide-induced in?ammatory cytokine production and expression of NLRP3 (NACHT, LRR, and PYD domain-containing protein 3) in?ammasome in human macrophages, inhibit the in?ammatory process, reduction of leukocyte adhe-sion, as well as proin?ammatory cytokines, increase in phagocytic and proliferative activity of the reticuloendothelial system, A. vera directly inhibits the cyclooxygenase pathway and reduces prostaglandin E2 production, which plays an important role in in?ammation, Intestinal absorption, drug absorption enhancement for drugs with low bioavailability due to extensive ef?ux, POAL (probiotics originating from Aloe leaf) strains; these and exhibit discriminative resistance to a wide range of antibiotics, A. vera gel has been shown to contain ?ve phytosterols, which are able to reduce visceral fat accumulation, and in?uences the metabolism of glucose and lipids in animal model experiments, where they reduced large-sized intestinal polyps and ameliorated reduction in plasma A. vera extract were able to reduce signi?cantly the transepithelial electrical resistance of the Caco-2 cell monolayers and thereby showed the ability to open tight junctions between adjacent cells

Author: Arshad H. Rahmani,1 Yousef H. Aldebasi,2 Sauda Srikar,1 Amjad A. Khan,3 and Salah M. Aly1,4

Treatment based on natural products, pivotal role in the treatment of diseases via modulation of biochemical and molecular pathways, aloe vera plays a therapeutic role in health management, Aloe vera in health maintenance based on its modulation of various biological activities, Pharmalogical effects of Aloe vera and its constituents in curing diseases via modulation of biological activities, Aloe vera, used therapeutically, plays a vital role in the immune system, as shown by the increased cell viability of macrophages, and also functions effectively in the first line of defense against pathogens, acemannan stimulates macrophage cytokine production, nitric oxide release, surface molecule expression, and cell morphologic changes

Author Abolfazl Aslani, Alireza Ghannadi, Razieh Raddanipour

design and evaluate the formulation of Aloe vera chewing gum with an appropriate taste and quality with the indications for healing oral wounds, such as lichen planus, mouth sores caused by cancer chemotherapy and mouth abscesses as well as reducing mouth dryness caused by chemotherapy, Aloe vera powder, the carbohydrate content was determined according to mannose and phenolic compounds in terms of gallic acid, chewing gum was cut into pieces of suitable sizes. Weight uniformity, content uniformity, the organoleptic properties evaluation, releasing the active ingredient in the phosphate buffer (pH, 6.8) and taste evaluation were examined by Latin square method, healing properties of Aloe vera improve the skin which is exposed to ultraviolet (UV) and gamma rays. It has antiinflammatory, antiseptic, antiviral, antibacterial, antitumor, moisturizing, antiaging, hypoglycemic, antidiabetic, cytotoxic, and antioxidants effects. It is also used against cardiovascular diseases, pharmaceutical chewing gums are produced in a solid form and a single dose. Their base mainly consists of gum base. This form of medication contains one or more active ingredients that are released by chewing. Pharmaceutical applications of pharmaceutical chewing gums include topical treatment of oral diseases and systemic delivery after absorption through the buccal mucosa or the gastrointestinal route, benefits of chewing gum include consumption without water ,high acceptance by children,[10] low side effects, suitable stability, high bioavailability, rapid onset effect[10] and relieving the mouth dryness by stimulating saliva, formulation of pharmaceutical chewing gums contain pharmaceutical active ingredients, gum bases, fillers, elastomers, plasticizers, softeners, emulsifiers, sweeteners and flavors, factors affecting drug release in this type of dosage form include physicochemical properties of the active ingredient, chewing gum properties and related factors with strength and number of masticatory movements, some of the formulated drugs in the form of chewing gum include fluoride, chlorhexidine, nicotine, aspirin, caffeine, and dimenhydrinate, oral Aloe vera can be used as a wound healer for oral wounds, To heal mouth sores, such as lichen planus, ulcers and abscesses caused by cancer chemotherapy, oral products such as mouthwash are used. Recently, one study examined the effects of 70% Aloe vera extract in the form of mouthwash for the treatment of mucositis caused by radiotherapy and another study examined the effects of 80% Aloe vera extract in the form of mouthwash to treat lichen planus

Author Alonso M, Támbara Y, López M, Aguilar JC, Mayo O, Prieto E, Cremata, J, Gerwig, G, Kamerling, H, Hardy E. (2012)

polysaccharide is a long chain polymer made of acetylated mannose units, which are held together by ?(1?4) linkages [1], inhibition of cellular proliferation with autonomous character (antitumoral and anticancerous action), antiviral action against a variety of viruses (e.g., herpes simplex, newcastle, measles, and HIV), stimulative and immunomodulatory direct effect on the immune system, the acemannan polymer has been intended for the treatment of cancer, viral diseases, breathing illnesses, as well as for infl ammations and infections, acemannan has been proposed as an adjuvant of other medications, polysaccharide as an adjuvant of antigens administered by means of the oral and parenteral routes, formulation for vaccine administration via the nasopharyngeal route whose main components are the surface antigen from the hepatitis B virus (HBsAg) and the acemannan polymer, adjuvant for the nasal administration of other soluble antigens of different nature, Immunopotentiative capacity of acemannan

Author Oliver Grundmann , BPharm,ms,PHD

properties of Aloe vera, promote the health of society, Clinical trial, improve skin integrity, retain skin moisture and integrity, Magnesium lactate available in the gel can prevent the production of histamine that causes itching and irritation of the skin, enhances the immune system and the synthesis of cytokines. Aloe vera is effective in inhibiting inflammatory reactions by the inhibition of IL-6 and IL-8, the reduction of leukocyte adhesion, an increase of IL-10 levels, and decrease of TNF alpha levels, Its regenerative properties are due to the compound glucomannan, which is rich with polysaccharides like mannose. Glucomannan affects fibroblast growth factor receptors and stimulates their activity and proliferation, which in turn increases the production of collagen

Authors S. Selvadurai, S.Divya, A.Geetha, K.Rohini and S.Anbazhagan

use of natural excipients to deliver the bioactive agents, natural excipients are their being non-toxic, less expensive and freely available, performance of the excipients partly determines the quality of the medicines, substantial evolution from an inert and cheap vehicle to an essential constituent of the formulation, Excipients are any component other than the active substance(s) intentionally added to formulation of a dosage form, herbal excipients which , conventional dosage forms, novel drug delivery systems, controlled delivery, Excipients are primarily used as diluents, binders, disintegrants, adhesives, glidants and sweeteners in conventional dosage forms like tablets and capsules, researchers in herbal excipients, natural ingredients in food, drugs, and cosmetics as they believe that anything natural will be more safe and devoid of side effects, natural excipients can potentially influence the rate and/or extent of absorption of a drug, herbal excipients are non-toxic and compatible, have a major role to play in pharmaceutical formulation, herbal excipients used in NDDS, Natural polysaccharides are extensively used for the development of solid dosage forms, polymers of monosaccharides (sugars) as aloe vera polysaccharides, highly stable, safe, non-toxic, and hydrophilic and gel forming in nature, linear polysaccharides remain intact in the physiological environment of the stomach and the small intestine, but are degraded by the bacterial inhabitants of the human colon which make them potentially useful in targeted delivery systems to the colon, Polymeric hydrogels are widely used as controlled-release matrix tablets, coat of considerable thickness was required to protect the drug core in simulated in vivo condition, matrix tablets, aloe vera powder spray drying technique, matrix patch for transdermal, design oral controlled drug delivery systems for highly water-soluble drugs using aloe vera as a carrier, colon-delivery systems, carrier in the form of a compression coating over the drug core, design oral controlled drug delivery systems for highly water-soluble drugs, carrier in the form of three-layer matrix tablets, formulations meant for daily administration, wet granulation technique, topical pharmaceutical formulations as a suspending and emulsifying agent, preparation of pastilles and lozenges and as a tablet binder, pellets, monolithic osmotic tablet system (MOTS), release-controlling agents in producing directly compressed matrices, mucoadhesive tablets, buccal delivery, Compaction and compression properties, pellets were prepared by extrusion-spheronisation

Author: Habibur RAloe Vera High Molecular Polysaccharidesan

health benefits associated with Aloe vera have been attributed to the polysaccharide contained in the gel of the leaves. On the other hand, the important pharmaceutical applications such as the use of the dried Aloe vera gel powder as an excipient in sustained release (SR) pharmaceutical dosage forms, development of water insoluble compound into a sustained release matrix tablets and the influence of Aloe vera gel powder in the dissolution and other physical properties of the SR matrix tablets were assessed. The HPMC and ethyl cellulose were used as polymer and different concentration of Aloe vera gel powder used as dissolution enhancer. Sustained release matrix tablets were formulated by direct compression method, developed tablet formulation complies with the monograph. The results suggest that Aloe vera is improved the dissolution of curcumin. Dissolution kinetics suggests that all the formulation followed Korsemayer Peppas model via anomalous diffusion mechanism. To conclude the Aloe vera gel powder can be used as dissolution enhancer for improving the drug absorption of water insoluble drugs.

Author Erica Españo,Jiyeon Kim and Jeong-Ki Kim

Aloe barbadensis, Aloe vera, antivirals, adjuvants, immunomodulator, phytochemicals, aloe emodin, aloin, acemannan, natural products, viral outbreaks, Plants, primary sources of new bioactive compounds, novel bioactive compounds, acetylated mannans, immunomodulatory effects, antiviral activities, Aloe Compounds for the Regulation of Immune Responses to Viral Infection, innate immune cells, anti-inflammatory activity, Immunomodulatory effects of Aloe vera components, Aloe vera have the ability to enhance the immunity and protectivity conferred by viral vaccines

Authors : Bianca Peterson, Morné Weyers , Jan H. Steenekamp, Johan D. Steyn, Chrisna Gouws and Josias H. Hamman *

bioenhancer; cytochrome P450; drug absorption enhancer; efflux; metabolism; P-glycoprotein; pharmacokinetic interaction; tight junction, new chemical entities are discovered with high therapeutic potential, compounds exhibit unfavorable pharmacokinetic properties due to poor solubility and/or poor membrane permeation characteristics, lipid-like barrier imposed by epithelial mucosal layers, crossed by drug molecules in order to exert a therapeutic effect, pre-systemic metabolic degradation of drug molecules, mainly by cytochrome P450 enzymes located in the intestinal enterocytes and liver hepatocytes, nasal, buccal and pulmonary routes of administration avoid the first-pass effect, they are still dependent on absorption of drug molecules across the mucosal surfaces to achieve systemic drug delivery, Bioenhancers (drug absorption enhancers of natural origin), systemic blood circulation by means of modulating membrane permeation and/or pre-systemic metabolism, natural bioenhancers and their main mechanisms of action for the nasal, buccal, pulmonary and oral routes of drug administration, poorly bioavailable drugs such as large, hydrophilic therapeutics are often administered by injections, Drug absorption is the process whereby drug molecules are transferred from the site of administration across biological membranes into the systemic blood circulation to produce a systemic pharmacological effect, biological cell membranes have a lipophilic nature due to their phospholipid bilayer structures, biological membranes, lipophilic properties to partition into the membranes in order to achieve passive absorption via the transcellular pathway, Adjacent epithelial/endothelial cells are connected by tight junctions, which are traversed by aqueous channels/fenestrae through which only small water-soluble molecules (<600 Da) can pass to get absorbed via the paracellular pathway, oral drug bioavailability besides drug permeation across the epithelial cells is pre-systemic metabolism or first-pass metabolism, which is the metabolism that takes place during uptake before the drug molecules reach the systemic circulation, Pre-systemic metabolism occurs mainly in the enterocytes of the gastrointestinal epithelium and the hepatocytes of the liver, molecules of natural origin that are capable of increasing the rate and/or extent at which co-administered drug molecules reach the systemic circulation unchanged (i.e., increased bioavailability), bioenhancers can improve the bioavailability of drug molecules include alteration of the plasma membrane fluidity to increase passive transcellular drug permeation; modulation of tight junctions to allow for increased paracellular diffusion; and active efflux transporter modulation, such as P-gp-related efflux inhibition, oral bioavailability of a drug molecule is determined by its ability to penetrate the gastrointestinal epithelial membrane, which is mainly determined by its physico-chemical properties (e.g., pKa, lipophilicity, molecular size, charge, dissolution and solubility), other factors that may affect the oral bioavailability of a drug include the gastric emptying rate, pH of the gastrointestinal fluid, interactions with other compounds (e.g., other drugs, food or herbs) and its affinity for active transporters, Plant (Aloe vera), Intercellular modulation, In vitro (Franz diffusion cells), Tight junction modulation, Ex vivo (rat intestinal tissue), In vitro (Caco-2 cells 2), Local mucosal tissue modulation, In vivo (human), Vitamin C and E: Ascorbic acid, tocopherols, tocotrienols, Metabolism inhibition; tight junction modulation,In vitro (Caco-2, LS180 cells 3), In vivo (rat) Indinavir: Antiviral protease inhibitor

Authors Jannes van der Merwe, Jan Steenekamp, Dewald Steyn and Josias Hamman

solubility; bioavailability; excipients; dissolution, active pharmaceutical ingredients (APIs), poor solubility and low dissolution rates, luminal fluids of the gastrointestinal tract, excipients can be incorporated in the formulation to assist in the dissolution process of the drug, selected excipients (e.g., alkalinizing agents, surfactants and sugars), formulations to increase the dissolution rate as well as specialized dosage forms such as self-emulsifying delivery systems and formulation techniques such as inclusion complexes and solid dispersions, drug solubility and bioavailability enhancement, active pharmaceutical ingredients; APIs) are usually not administered to patients on their own as single compounds, formulated into carefully designed dosage forms, accurate dosing, quality, efficacy, safety, stability as well as high patient acceptance and compliance, dosage forms were made by simply adding pharmacologically inert substances (also referred to as excipients), selection and production of excipients that fulfil specific functions, beyond just making up volume, such as assisting in production of the dosage form and optimizing drug delivery from novel dosage forms, functions of excipients in dosage forms are related to all the different aspects of the final product including its manufacturability, the stability of the API, dose uniformity, effective delivery of the API to the systemic circulation after administration as well as acceptable organoleptic properties , Pharmaceutical excipients are usually included in dosage forms in larger quantities than the API and can make up to about 90% of the total mass/volume of medicinal products, The International Pharmaceutical Excipient Council (IPEC), different classes of pharmaceutical excipients, regulatory requirements for pharmaceutical excipients, new chemical excipients, existing excipients that are modified with respect to purity and/or physical properties such as particle size, co-processed excipients’ (i.e., two or more existing excipients which are formulated into a new excipient with physical properties, excipients that are chemically modified, development of novel drug delivery systems, sophisticated excipients are needed to impart certain properties, fulfil multiple roles in a dosage form or drug delivery system, high functionality excipients, single excipient that provides additional functions to innovative drug delivery systems to improve the overall performance of the product with significant economic benefits, provide better flow, act as a disintegrant and simultaneously allow a higher drug loading in the dosage form due to its high compressibility, functional excipients are needed to assist in overcoming their poor physico-chemical properties, Specialty excipients are used to produce dosage forms that can reduce the number of doses by modifying the rate of drug release or improve drug delivery by targeting drug release in a specific region in the gastrointestinal tract where drug absorption is the highest. Functional excipients are also used to re-formulate existing drugs in order to produce more effective products that are more cost-effective, Aqueous solubility and membrane permeability, Biopharmaceutics Classification System (BCS), influence the bioavailability of a drug, many promising new drugs exhibit poor solubility, and some also exhibit poor membrane permeability, a drug that exhibits an aqueous solubility lower than 0.1 mg per mL is likely to experience limited bioavailability, and its rate of absorption will be governed by the dissolution rate, improve the solubility of these drugs include formation of pro-drugs, formation of salts, co-precipitation, solvent evaporation and size reduction (or micronation), Formulation strategies, melt extrusion/granulation, formation of solid dispersions and formation of inclusion complexes. Furthermore, excipients such as surfactants, polymers, super-disintegrants and multifunctional fillers have been included in dosage forms to increase the apparent solubility of drugs, solubility/dissolution and/or membrane permeation/absorption and thereby also the bioavailability of poorly soluble APIs., aloe vera as functional vehicle excipient for dietary supplements.

Author Narayana Charyulu Rompicherla , Punam Joshi 1, Amitha Shetty, Kalvatala Sudhakar ,Hawraz Ibrahim M. Amin , Yachana Mishra, Vijay Mishra , Aqel Albutti * and Naif Alhumeed

Topical treatments are a potential therapeutic option for the therapy of osteoarthritis, with significant data supporting the effectiveness and safety of topical formulation. Topical gel formulations may offer an alternative to oral formulations to relieve osteoarthritis (OA) pain while decreasing systemic exposure. Topical capsaicin transemulgel may represent an effective and safe alternative. The transemulgel was prepared from aqueous Aloe vera gel and Carbopol 934 with capsaicin in clove oil emulsion, improved permeability properties. The formulation caused no skin irritation when applied topically, emulsion, capsaicin, arthritis, topical, anti-inflammatory agent, drug delivery, Osteoarthritis is the most common degenerative joint disease, Pathological changes in osteoarthritis joints include destruction of articular cartilage, progressive loss, subchondral bone thickening, osteophytes formation, ligament degeneration, menisci of the knee, and hypertrophy of the joint capsule, treatment includes oral and topical pharmacological agents, patient education, alternative surgery, medicine, physical therapy, and modalities, topical drug delivery has advantages over conventional routes; in particular, it avoids first-pass metabolism, and is a non-invasive mode of drug delivery with a sustained and controlled release profile, Aloe vera (Aloe barbadensis miller), a perennial plant belonging to the family Liliaceae, is used due to its anti-inflammatory, anticancer, antimicrobial, immunomodulatory, and burn healing effects. It has been used in different commercial products, due to its cooling effect, the burning sensation of capsaicin can be reduced by rubbing the skin with Aloe vera gel as a base ,therefore, the present research work aimed to develop and evaluate capsaicin transemulgel using Aloe vera gel as a base for the treatment of osteoarthritis

Author S. Maru, Sudarshan Singh, Shree H. N. Shukla

Mucilages are complex polymeric substances that are carbohydrates in nature and have garnered considerable interest in the food, pharmaceutical, and cosmetic industries for their functional, health, and nutritional benefits, polysaccharide macromolecules that form intricate molecular networks capable of retaining large amounts of water, making them a potential source of natural hydrocolloids that provide a substantial thickening effect that is desirable for the chemical and cosmetic industries, polysaccharides have medicinal attributes such us wound, burn, and ulcer healing, as well as antidiabetic and antiglycation effects, other mucilage applications include its use in foods as a stabilizer, flavoring agent, fat substitute, and edible coating to extend the useful life of fruit, biological activities, including antiviral, antibacterial, laxative, radiation protection, wound healing, antioxidant, anti-inflammatory, anticancer, antidiabetic, antiallergic, and immunostimulatory effects, among others, have been attributed to the aloe vera mucilage (AV mucilage)

Author: Endang Diyah Ikasari*, Anang Budi Utomo, Hanny Setyowati

polymer for pharmaceutical industry, Aloe vera gel may be employed to effectively deliver poorly absorbable drugs through the oral route of drug administration. Ranitidine hydrochloride is a drug of choice in the treatment of ulcer. The drug has a short biological half-life of approximately 2-3 hours, thus a sustained release dosage form of ranitidine HCl is desirable. The aim of this study was to compare Aloe vera gel and Aloe vera powder as polymer mucoadhesive. The obtained results indicated that aloe vera powder has physical properties better than aloe vera gel. Drying process of aloe vera powder is important to improve their stability which performed by less of moisture content, increase of flow rate, swelling index, in vitro mucoadhesive, and dissolution. Aloe vera powder is a suitable polymer for local delivery in the gastrointestinal tract.

Authors Jun Wu ,Ying Zhang,Zhongming Lv,Ping Yu,Weiqing Shi

Aloe vera has been widely used in health and nutritional supplements, Aloe vera soft capsule (ASC), safety evaluation of Aloe vera products before marketing, aloe vera not produce any marked subacute toxic effects, ASC showed no mutagenic activity in the Ames test and no evidence of potential to induce bone marrow micronucleus or testicular chromosome aberrations in ICR mice exposed to 10000 mg/kg bodyweight. Collectively, ASC could be considered safe before it was marketed as a laxative and moistening health food.

Author Kharat Amol* and Pawar Pratibha

Novel drug delivery system is the method by which a drug is delivered can have a significant effect on its efficacy. Some drugs have an optimum concentration range within which maximum benefit is derived, and concentrations above or below this range can be toxic or produce no therapeutic benefit at all. From this, new ideas on controlling the pharmacokinetics, pharmacodynamics, nonspecific toxicity, immunogenicity, biorecognition, and efficacy of drugs were generated, A novel drug delivery system is a system that offers multiple drug delivery solutions such as Oral Drug Delivery Systems and Materials, Parenteral and Implant Drug Delivery Systems, Pulmonary and Nasal Drug Delivery, transmucosal Drug Delivery, Transdermal and Topical Drug Delivery, Delivery of Proteins and Peptides, Drug Delivery Pipelines, Drug Delivery Deals, Novel drug delivery system is a novel approach to drug delivery that addresses the limitations of the traditional drug delivery systems. Modern medicine cures a particular disease by targeting exactly the affected zone inside a patient’s body and transporting the drug to that area. Determination of pharmacokinetics, mechanism of action, site of action, accurate dose required , Types of novel drug delivery systems, Sublingual that is, a drop under the tongue, Self adhesive patch on skin, Pump e.g. Insulin pump, Special pervious plastic injected below skin e.g. Norplant, recent developments in novel drug delivery system of herbals, Phytosome, Liposome, nanoparticles, Emulsions, Microsphere, Ethosome, Solid lipid nanopartical, Controlled Drug Delivery System, Other novel vesicular herbal formulations, Proprietary novel drug delivery system of plant actives and extracts, Niosomes, Proniosomes, Transdermal Drug Delivery System, Dendrimers, Liquid Crystals, Hydrogels, development of novel drug delivery systems (NDDS) for plant actives and extracts, Ocusert is a long-acting sustained-delivery system used as ocular insert for the treatment of open-angle glaucoma. Ocusert consists of pilocarpine as miotic drug. Pilocarpine is obtained from the leaves of Pilocarpus microphyllus and other species. A soft contact lens soaked in pilocarpine solution also provides sustained delivery, Hair-growth herbal spray contains pure, natural traditional Chinese medicine including ginseng extract, Chinese angelica extraction, and Polygonum multiflorum extraction. It is made with efficient active constituent extracted by advanced super-critical fluid-extract (SFE) technology with high-tech bioengineering CO 2 super-critical fluid. Hair-growth herbal spray contains pure, natural TCM enhancer Angelica naphtha Its functions are Influence the keratodermia hydration, Dissolve sebum within sebaceous gland duct, Novel drug delivery system in herbals, formulation of Novel drug delivery system in herbals.

Author Thanushree HR, Kumar GBK, Acharya A.

Diclofenac sodium has many side effects like nausea, vomiting, GIT disorders. These side effects can be reduced by converting into emulgel formulations. The emulgel formulation of Diclofenac Sodium was prepared by incorporation method, using span 20 and tween 20 as nonionic surfactants, clove oil and cinnamon oil as penetration enhancers, Aloe vera as a gel base and sesame oil as a solvent. The prepared emulgel formulations were evaluated for compatibility study, physical examination, viscosity, spreadability, in vitro diffusion studies, various release kinetic studies and stability studies. In vitro diffusion studies were carried out using cellophane membrane, results showed that emulgel formulations (F2-F7) showed higher cumulative percent drug release (49-65%) compared to normal gel (48%) and marketed gel (35%). Results of in vitro diffusion studies showed that formulation F3 and F6 exhibited 64% and 65% drug release respectively over a period of 6 hrs. In conclusion, a physiochemical stable diclofenac emulgel was formulated, which could deliver significant amount of drug across the skin in steady-state manner for the prolong period of time in the treatment of osteoarthritis.

Author: A. Shirwaikar*, Annie Shirwaikar1, S. Lakshmana Prabu and G. Aravind Kumar

use of natural excipients to deliver the bioactive agents has been hampered by the synthetic materials. However, advantages offered by these natural excipients are their being non-toxic, less expensive and freely available. The performance of the excipients partly determines the quality of the medicines. The traditional concept of the excipients as any component other than the active substance has undergone a substantial evolution from an inert and cheap vehicle to an essential constituent of the formulation. Excipients are any component other than the active substance(s) intentionally added to formulation of a dosage form, Polysaccharides, volatile oils, controlled delivery, Excipients are primarily used as diluents, binders, disintegrants, adhesives, glidants and sweeteners in conventional dosage forms like tablets and capsules, Present day consumers look for natural ingredients in food, drugs, and cosmetics as they believe that anything natural will be safer and more devoid of side effects, excipients are inert and do not exert any therapeutic or biological action or modify the biological action of the drug substance has changed and it is now recognized that excipients can potentially influence the rate and/or extent of absorption of a drug. As herbal excipients are non-toxic and compatible, they have a major role to play in pharmaceutical formulation. Hence, this paper is an attempt to review herbal excipients used in NDDS, Polysaccharides in Pharmaceuticals, Natural polysaccharides are extensively used for the development of solid dosage forms. These polymers of monosaccharides (sugars) are inexpensive and available in a variety of structures with a variety of properties. They are highly stable, safe, non-toxic, and hydrophilic and gel forming in nature, Pectins, starch, guar gum, amylase and karaya gum are a few polysaccharides commonly used in dosage forms. Non-starch, linear polysaccharides remain intact in the physiological environment of the stomach and the small intestine, but are degraded by the bacterial inhabitants of the human colon which make them potentially useful in targeted delivery systems to the colon

Authors: Hindustan Abdul Ahad, Sreeramulu J, Hima Bindu V, Chitta Suresh Kumar, Kishore Kumar Reddy B, Chandana Rekha V , Sivaji S

develop matrix tablets of Glimepiride with Aloe barbadensis miller leaves mucilage and Povidone and to study its functionality as a matrix forming agent for sustained release tablet formulations, mucilage of Aloe barbadensis miller leaves clinically and experimentally proved anti-diabetic activityand release retardant activity, Glimepiride is an oral hypoglycemic agent, which is commonly prescribed for the treatment of patients with type II diabetes mellitus , It belongs to sulfonylureas drug class. Glimepiride is a weak acid with PKa of 6.2, glimepiride is practically insoluble in water and acidic environment but highly permeable (class 2) according to the Biopharmaceutical classification System (BCS) , the oral absorption is uniform, rapid and complete with nearly 100% bioavailability therapy with Glimepiride is usually initiated with 1 to 2 mg, the pharmacokinetics and dosage schedule supports once daily sustained release formulations for Glimepiride for better control of blood glucose levels to prevent hypoglycemia, enhance clinical efficacy and patient compliance ,the objective of present investigation is to design and evaluate sustained release tablets of Glimepiride using Aloe barbadensis miller leaves mucilage and Povidone combination as release retardant for making sustained release matrix tablets.

Author Hongyu Zhong, Xiang Li, Wanqi Zhang, Xiaoxiao Shen, Yuangang Lu and Hongli Li

Acne is a chronic disorder that affects almost 80% of adolescents and young adults, causing psychological and emotional distress, Acne is a chronic disorder of pilosebaceous units, which is characterized by comedones, inflammatory papules, pustules, cysts, and nodules, affecting almost 80% of adolescents and young adults, acne lesions can result in post-inflammatory hyperpigmentation (PIH) and scarring, inflammation exists throughout the whole cycle of acne lesions, and PIH can cause psychological and emotional distress, leading to a great influence on healthy quality of life in affected individuals, the current treatments include topical and systemic medications for moderate to severe acne, however, their curative effects are limited due to adverse effects and unsatisfactory efficacy, the current treatments for acne are either ineffective or have many side effects, enhanced the absorption of aloe vera gel, and soft mask to make a purely physical method without any drugs, In recent years, there have been an increasing number of medicines and cosmetics made from aloe vera gel (AVG), the mucilaginous tissue in the center of the aloe vera leaf , its pharmacological functions include antibacterial, anti-inflammatory effects and wound healing promotion (16–18). A previous study suggested that Aloe Vera Gel treatment in combination with tretinoin was effective in reducing non-inflammatory and inflammatory acne lesions. In both the treatment group and control group, the number of papules/pustules and the area of hyperpigmented lesions were counted, and a smart mirror intelligent face system was used before and after the combined therapy, combined therapy with aloe vera significantly reduced the number of papules and the area of hyperpigmented lesions and improved skin roughness and local blood circulation, is a method for patients who seek topical treatments with mild side effects and low antibiotic resistance rates.

Author: E. Leucuta, Sorin

Activation-modulated DDS; Biodegradable Systems; Drug delivery systems; Enzyme Activated; Hopfenberg Model; Microreservoir Partition Controlled DDS; Osmotic Pressure Activated DDS; Polymer Matrix-diffusion DDS; medicine; modified release; pharmacy, new generations of pharmaceutical systems: medicines with extended release, controlled release pharmaceutical systems, pharmaceutical systems for the targeted delivery of drug substances. The latest advances and approaches for delivering small molecular weight drugs and other biologically active agents such as proteins and nucleic acids require novel delivery technologies, the success of a drug being many times dependent on the delivery method. All these dosage forms are qualitatively superior to medicines with immediate release, in that they ensure optimal drug concentrations depending on specific demands of different disease particularities of the body. Drug delivery of these pharmaceutical formulations has the benefit of improving product efficacy and safety, as well as patient convenience and compliance, biopharmaceutical, pharmacokinetic, pharmacologic and technological principles in the design of drug delivery systems with modified release as well as the formulation criteria of prolonged and controlled release drug delivery systems. pharmaceutical prolonged and controlled release dosage forms intended for different routes of administration: oral, ocular, transdermal, parenteral, pulmonary, mucoadhesive, but also orally fast dissolving tablets, gastroretentive drug delivery systems, colon-specific drug delivery systems, pulsatile drug delivery systems and carrier or ligand mediated transport for site specific or receptor drug targeting. Specific technologies are given on the dosage forms with modified release as well as examples of marketed products

Author: Zaira López,Gabriela Núñez-Jinez,Guadalupe Avalos-Navarro,Gildardo Rivera,Joel Salazar-Flores,José A. Ramírez,Benjamín A. Ayil-Gutiérrez,and Peter Knauth

supplements from Aloe vera, concentrated powders (starting products), final product at a concentration of 1x, meaning g/L for decolorized and spray-dried inner leaf powder (ILG), Aloe fillet, Aloe gel, thick watery inner parenchyma, secondary metabolites such as complex polyphenols (e.g., tannins and flavonoids), lignins, saponins, anthraquinones, glycoproteins, polysaccharides, and enzymes and also smaller metabolites, like sterols, fatty acids, alcohols, vitamins, amino acids, and saccharides, Aloe gel consists of about 99% water; the residual dry mass is composed of approximately 35.5% crude fibres, 26.8% soluble saccharides, 23.6% ashes (minerals), 8.9% proteins, and 5.1% lipids, More than 95% of the soluble saccharides are glucose; the non-starch polysaccharides (apart from pectin, cellulose, and hemicellulose) consist mainly of mannose, glucose, and galactose, forming ??1,4-linked polymers of 30–40 kDa, Aloe extracts as a supplement for functional food no negative health effects could be observed when the extract was decolorized (i.e., treated with charcoal to eliminate anthranoids), antraquinones, aloe emodin, aloin a, aloin b, remotion with adsorbent activate charcoal, filtered through diatomaceous earth, and dehydrated by spray-drying , AMB Wellness starting products (powders) INNOVALOE from its facilities in Mexico, which are commercialized as food supplements of A. vera , spray-drying: 200x inner leaf gel (ILG) powder or the inner leaf fillet, (<10% of polysaccharide acemannan)

Author K Sharma

hypertension is a chronic disease, which requires long-term treatment with drug therapy at steady state drug blood concentration. Candesartan cilexetil (CC) is a prodrug that is rapidly converted to candesartan (its active metabolite) during absorption from the gastrointestinal tract and confers blood pressure lowering effects by antagonizing the hypertensive effects of angiotensin II. It has a molecular weight of 610.66 with poor oral bioavailability, the patients requiring further reduction in blood pressure should be titrated to 32 mg, the major disadvantages of such a drug therapy are more frequency of administration, extensive first pass metabolism and variable bioavailability which make it an ideal candidate for transdermal drug delivery systems. This explains the need of anti-hypertensive transdermal patches in the perspective of enhancing the bioavailability as well as in improving patient compliance Transdermal drug delivery system allows delivery of contained drug into the systemic circulation via permeation through skin layers at a controlled rate. These systems are easy to apply and remove as and when desired. However, the protective upper layer of the skin, stratum corneum (SC) behaves like a challenging barrier for the penetration of majority of drugs, It offers a formidable physical barrier to molecular transport, This layer is very specific with regards to the type of molecule that can be transported across the skin, and therefore, only molecules with certain physicochemical properties can readily cross the skin, this limits the range of potential drugs that can be administered transdermal, which emphasizes the need for formulations to incorporate penetration enhancers to assist in the effective delivery of a larger variety of drugs across the skin, the use of herbal penetration enhancers which penetrate into human skin and shows reduction in the barrier resistance is widely accepted in transdermal drug delivery. The mechanism behind enhanced penetration rate of drugs across the skin is through two possible mechanisms of action. First, the penetration enhancer can work by altering the solubility properties of the skin, thereby increasing the solubility of the drug within the SC; second, the enhancer disrupts the ordered nature of the skin lipids, which consequently influences diffusion across the SC, Nowadays, many herbal penetration enhancers are included in generally recognized as safe substances list, and they possess low side effects and irritancy in comparison with synthetic chemicals such as solvents and azones or surfactants, One such a natural product, Aloe vera (Aloe barbadensis Miller) gel, has shown potential to enhance the permeation of certain drug molecules through skin membranes. Aloe Vera Gel gel is the viscous, transparent, and colorless mucilaginous gel obtained from the parenchymatous cells in the fresh leaves. It was suggested that the mucilaginous gel of the aloe, consisting mainly of polysaccharides, holds the secret to some of the medicinal properties and biological effects of this family of plants, which was confirmed for drug absorption enhancement across intestinal epithelial cells. Aloe Vera Gel has an element called “Lignin” which helps it to penetrate right down to the cellular level. It also has another element called “Saponin” which works as a natural cleansing agent. Both these elements working in conjunction reach the cellular level of the skin. In addition to this, it also nourishes the skin and replenishes it with the much-needed nutrition that it requires, s, it increases the in vitro skin penetration of some compounds depending on their molecular weights with an apparent inverse correlation between enhancement ratio and molecular weight of the compound. This penetration enhancement effect of the aloe gel was explained by a probable pull effect of complexes formed between the compound and the enhancing agent within the aloe gel but it was stated that the proposed mechanism of action

Author: Saidin, N.M., Anuar, N.K., Meor Mohd Affandi, M.M.R.

polysaccharides used in transdermal drug delivery system, system provides continuous controlled delivery of active ingredients through human skin and into the blood stream, Poor penetration of most drugs into the skin, increase the permeability of such drugs, natural polysaccharides in transdermal formulations has increased as an alternative to the synthetic materials, Structure modification and polymer blending polysaccharides and other materials in order to alter their functional properties, natural polymers provided better controlled release and drug permeation, physicochemical properties of polysaccharides and their effects on drug release profile, skin microstructure, and transdermal drug permeation

Author Rishabha Malviya, Pranati Srivastava and G.T. Kulkarni

With the increasing interest in polymers of natural origin, the pharmaceutical world has compliance to use most of them in their formulations. Moreover, the tremendous orientation of pharma world towards these naturally derived polymers has become a subject of increasing interest to discover, extract and purify such compounds, mucilage, as a potent candidate to be used in various pharmaceutical formulations, Natural polymer Pharmaceutical application Pharmaceutical excipient, plant derived polymers have mucilages can occur in high concentrations in different evoked tremendous interest due to their diverse pharmaceutical applications such as diluent, binder, disintegrant in tablets, thickeners in oral liquids, protective colloids in suspensions, gelling agents in gels and bases in suppository, also used in cosmetics, textiles, paints and paper-making, these polymers such as natural gums and mucilage are biocompatible, cheap and easily available and are preferred to semi synthetic and synthetic excipients because of their lack of toxicity, low cost, availability, soothing action and non irritant nature, Polysaccharide hydrocolloids including mucilages, gums and glucans, polysaccharides constitute a structurally diverse class of biological macromolecules with a broad range of physicochemical properties which are widely used for various applications in pharmacy and medicine, Mucilages are most used as adjuvant in pharmaceutical preparations, with wide range of applications such as thickening, binding, disintegrating, suspending, emulsifying, stabilizing and gelling agents. Mucilages may be used as sustained and controlled release formulations , binding agent in pharmaceutical formulations, Gelling Agent, Suspending Agent, Disintegrant, Sustained Release Polymer

Authors Prashant Singh*, Tarique Mahmood, Arshiya Shameem, Paramdeep Bagga, Nesar Ahmad

Herbal or natural excipients have a great advantage over their synthetic analogues, herbal excipients, which are manly polymers of natural origin, the pharmaceutical industries are getting more inclined towards their use in formulation development, natural excipients which can be proposed to be used as diluent, binder, disintegrant as well as lubricant in various types of formulations as they are biocompatible and capable of giving additional nutrition to the developed dosage form

Author: Tafara Jambwa, Alvaro Viljoen, Josias Hamman

pharmaceutical industry endeavours to develop novel drug delivery systems which require excipients that full specific functions. Excipients from renewable sources are attractive due to their sustainable mass production. The purpose of this study is to investigate the potential use of gel and whole leaf materials from Aloe vera as excipient in the formulation of controlled release matrix-type mini-tablets, Matrix-type mini-tablets manufactured from the aloe materials alone, and in combination with other polymers were evaluated in terms of their physical characteristics, mucoadhesive properties, swelling behavior and drug release kinetics. Some of the formulations exhibited high potential to control drug release from matrix-type tablets and some approached zero-order kinetics, A disadvantage of the conventional immediate-release tablet as dosage form is that drug plasma levels fluctuate over successive doses, ,modification in drug-release rate, such as controlled release, may be beneficial in eliminating the cyclic fluctuations in drug plasma levels , Polymers used in dosage form design can be classified as synthetic polymers, semi-synthetic polymers and polymers of natural origin, Natural polysaccharides are often obtained from plants in the form of mucilages and gums. In many cases, the properties of a natural polymer do not t the needs of a specific application and blending with a synthetic polymer can sometimes be used to achieve the desired properties , Multiple-unit dosage forms over several advantages over conventional single-unit dosage forms. They contain a number of sub-units in which the dose is the sum of the quantity of the drug in each sub-unit. Examples include granules, pellets or mini-tablets that can be formulated into a single, hard gelatin capsule, Formulations containing the different aloe powders individually, and in combination with either Carbopol® or hydroxypropyl methylcellulose in different ratios, aloe leaf materials are suitable as excipients in the design and development of matrix-type tablets for modified drug release, the formulation containing Aloe Vera Gel and Carbopol in a 50:50 ratio, indicating aloe vera gel powder has potential as excipients in combination with other polymers to form matrix systems that can control drug release

Author DAVID DAHLGREN

Before an orally administered drug reaches the systemic circulation, it has to dissolve in the intestinal fluids, permeate across the intestinal epithelial cell barrier, and pass through the liver, the permeation rate of drug compounds can be low and show regional differences, regional intestinal permeability values of model compounds in human, effects of absorption-modifying pharmaceutical excipients (AMEs) on the intestinal permeability of the model compounds, intestinal permeability, absorption-modifying excipients, nature of the gastrointestinal (GI) tract is to prevent absorption and translocation of potentially harmful luminal constituents into the central circulation, while still allowing the absorption of nutrients and water, obstacles associated with the oral administration route that need to be overcome for successful systemic drug treatment, drug product/formulation (e.g., capsule, tablet) must initially disintegrate, so that drug particles can dissolve in the GI fluid , The drug solubility in the intestinal GI fluids must be high enough to enable a sufficiently fast dissolution rate. The free drug molecules in solution also determine the concentration gradient between the intestinal lumen (i.e., the inside of the intestinal tube) and the blood; this gradient is the driving force for permeability and absorption, where permeability is the transport across the apical membrane, the rate limiting membrane barrier. A reduction in the luminal free drug concentration can occur if the drug molecule precipitates, is chemically or enzymatically degraded, or forms complexes with the luminal content. The drug molecules are considered absorbed after they have been transported across the outer lipophilic cell membrane, and this membrane can impose substantial resistance to large and/or hydrophilic drug molecules. Finally, before an absorbed drug molecule is introduced into the central blood circulation, it passes through the intestinal barrier and liver, where it may be metabolized and lose its pharmacological effect, or be excreted with bile back into the intestines , drug discovery process, candidate drug molecules are selected based on physicochemical properties, the affinity for the pharmacological target, membrane transport properties, chemical and metabolic stability, and their safety/toxicity profile, high cost is also associated with the high attrition rate in drug development, the high cost and attrition rate at the later stage of the drug-development process, 16% of all drug compounds that fail in the early phase of clinical development do so because of undesirable pharmacokinetic properties, development of formulations containing drugs with low intestinal solubility and/or low intestinal permeability, drug product can be designed to mitigate the impact of unfavorable PK properties, mass transfer of luminally dissolved drug molecules across the apical intestinal epithelial cell barrier includes one, or several, of the following transport mechanisms: passive lipoidal and paracellular diffusion, and/or carrier-mediated transport in both the absorptive and secretive (efflux) directions, Carrier-mediated (CM) transport is the process whereby a compound is transported into (influx) or out of (efflux) the intestinal epithelial cell cytosol across the lipoidal membrane bilayer using a protein transporter. CM transport can be either active or facilitated, Active transport uses energy to create a concentration gradient across membranes, and is classified as primary or secondary, CM transport is important for absorption of water soluble nutrients, such as glucose, vitamins, and amino acids, but this transport mechanism can also be important for drug compounds, dissolved drug molecule must diffuse across a water layer with limited convection covering the epithelial cell membrane before it can be absorbed

Author Zhang L, Tizard IR. Department of Veterinary Pathobiology, Texas A & M University College Station 77843, USA.

Acemannan, major carbohydrate fraction, aloe vera gel, acemannan could stimulate macrophage cytokine production, nitric oxide release, surface molecule expression, and cell morphologic changes, Macrophage activation RAW cells

Author Nicholas J Sadgrove 1, Monique S J Simmonds

Scientific studies of Aloe vera, therapeutic claims, breakage of acemannan chains into smaller fragments enhances biological effects, immune system to attack cancer cells by mannose receptor agonism of macrophage or dendritic cells, aloe vera oral consumption, small intestine or colon, dietary acemannan, acemannan is digested by microbes into short-chain fatty acids, closure of wounds, promotes granular tissue formation, macrophages or neutrophils, reversal of inflammation, and acceleration of the re-epithelialization process

Author: Gjylije Hoti,Adrián Matencio , Alberto Rubin Pedrazzo,Claudio Cecone,Silvia Lucia Appleton,Yousef Khazaei Monfared , Fabrizio Caldera andFrancesco Trotta

Nutraceuticals are bioactive or chemical compounds acclaimed for their valuable biological activities and health-promoting effects. The global community is faced with many health concerns such as cancers, cardiovascular and neurodegenerative diseases, diabetes, arthritis, osteoporosis, Delivery Systems for Nutraceuticals, A nutraceutical has not always met the requirements to achieve the therapeutic purpose, therefore, the systems for their delivery must be designated to produce products that have consistent quality attributes. The “biomaterials science” is considered as the focus toward the development of materials, tailored to a specific application, that can elicit highly precise reactions with proteins and cells. The biomaterials synthesis, characterization, testing, optimization, and the biology of host-material interactions are highlighted during the most intense investigation. The biomaterial must accomplish various requirements such as toxicology, biocompatibility, functional tissue structure, and pathobiology, mechanical and performance requirements, healing, industrial involvement, regulation, poor bioavailability is the major challenge in designing oral dosage forms. First-pass metabolism, aqueous solubility, dissolution rate, drug permeability, presystemic metabolism, and susceptibility to efflux mechanisms, are various factors on which the oral bioavailability depends, nutraceuticals bioavailability is an important, and an urgent necessity, because of the growth of health challenges, and rapid population, ?-carotene, vitamin E, various polyphenols such as phenolic acids, stilbenes, flavonoids, lignans, etc., are slowly absorbed, and therefore have a limited bioavailability,bioavailability is a property of the drug alone and its delivery systems. Low bioavailability of the drug on its therapeutic use can be considered safe for oral administration because it can be administered in excess without any adverse effects. To increase the bioavailability, the development of powerful drug delivery systems, for surviving the harsh acidic environments of the stomach and rising absorption through the intestinal wall, is considered, Bioaccessibility (B*), absorption (A*), and transformation (T*), are the three main stages that the studies on the nutraceutical bioavailability climax. Bioaccessibility, the first step is defined as the fraction of ingested nutraceutical that becomes accessible for absorption through the epithelial membrane of the intestine, whereas absorption, the second step, comprises biocomponent absorbed at the level of the gastrointestinal tract (GIT) epithelial cells. Further, transformation, the third step, describes the chemical or biochemical

Author: Bani Ahluwalia 1 2, Maria K Magnusson 1, Fredrik Larsson 2, Otto Savolainen 3 4, Alastair B Ross 3 5, Lena Öhman 1

immunomodulation, bioactive component(s), polysaccharides (acemannan), human blood T cell activity, T cell phenotype and proliferation, 1H-NMR spectroscopy, T cell activation, proliferation, apoptosis, and cell-death in vitro, metabolomics, metabolite profile, gas chromatography mass spectrometry (GC-MS) for metabolite profiling, The Effect of Aloe Extracts on T Cell Activity and Proliferation Is Correlated to Their Distinct Metabolite Composition, Aloe Extracts Differ in Their Metabolite Composition, Aloe metabolite profiles, Effect Cluster metabolites

Author Brown G.S.; Kelsey L.S.; Yates K.M.; Rosenberg L.J.; Talmadge J.E.

injectable acemannan, multiple therapeutic properties including activity in wound repair and as a biological agent for the treatment of neoplasia in animals as well as the ability to activate macrophages, hematoaugmenting properties, subcutaneous administration, increases splenic and peripheral blood cellularity, lymphocytes , monocytes and platelets, multiple cell lineages.

Author Garnick JJ, Singh B, Winkley G.

gel containing silicon dioxide, aloe vera, and allantoin in the healing of recurrent aphthous ulcers, parameters used to evaluate healing were number of lesions during a 3-to-4-month period, length of the interval between ulcers, size of ulcers, and pain from ulcers

Author: L. Bravo C

antioxidants, free radicals, flavonoids cardiovascular diseases, metabolism, diet, food, metals, molecular mass, nutritive value, plants, tannins , science of chemistry ,cancer prevention, metabolites, polyphenols, molecule, plant metabolites, phenolic molecules to highly polymerized compounds with molecular weights of greater than 30,000 Da, polyphenol, on protein digestibility, antioxidant capacity (free radical scavenging and metal chelating activities) and their possible beneficial implications in human health, dietary sources, metabolism, nutritional significance

Author: Panneerselvam Jithendra†, Abraham Merlin Rajam†, Thambiran Kalaivani, Asit Baran Mandal, and Chellan Rose*

aloe vera (AV), Collagen–Chitosan (COL-CS) scaffolds, composite preparations, complex composite, swelling property, hydrated condition, aloe vera concentration, enhanced growth and proliferation of fibroblasts, tissue engineering applications, scaffold or biomaterials that support cellular growth, differentiation, and migration, skin protector, and also detoxifying agent, Chitosan is a natural biopolymer, rough texture on a smooth surface

Author Liu, C.; Cui, Y.; Pi, F.; Cheng, Y.; Guo, Y.; Qian, H.

acemannan, considered one of the main bioactive polysaccharides of Aloe vera, possesses immunoregulation, anti-cancer, anti-oxidation, wound healing and bone proliferation promotion, neuroprotection, and intestinal health promotion activities, the biological activities of acemannan from Aloe vera determined by in vivo, in vitro and clinical experiments are summarized, and possible mechanisms of these bioactivities , use of acemannan in dentistry and wound healing, structure-activity relationships of acemannan and its medical applications, Polysaccharides are extensively used in various healthcare products and medicines because of their notable and excellent bioactivities, such as antimicrobial , antitumor antiviral, and antioxidant activities, polysaccharides are among the natural biopolymers, which are widely used as biomaterials for wound healing, drug delivery and tissue engineering , Aloe vera is one of the few natural plants that are very abundant in polysaccharides, acemannan-rich sponge was more easily absorbed than a complex inorganic material, and can also act as a scaffold to provide migration and attachment of cell growth factors, because the sponge can not only effectively fix the blood clot in orbit. Acemannan has a significant effect on the healing of alveolar bone and further promotes bone formation. This means that acemannan may be a natural biopolysaccharide material for bone regeneration

Author: Sam Maher, Luca Casettari ,and Lisbeth Illum

Drug delivery systems that safely and consistently improve transport of poorly absorbed compounds across epithelial barriers are highly sought within the drug delivery field. The use of chemical permeation enhancers is one of the simplest and widely tested approaches to improve transmucosal permeability via oral, nasal, buccal, ocular and pulmonary routes, absorption modifying excipients; nasal delivery; ocular delivery; oral delivery; permeation enhancers; transmucosal permeation; vaginal delivery, natural extracts from Aloe vera interact with intestinal epithelial cells. The study found whole leaf and gel extracts of Aloe vera contain considerable quantities of the acidifiers, citric acid and malic acid, which have previously demonstrated enhancement action, Extracts caused a partial reduction in TEER and a two- to three- fold increase in permeation of fluorescein isothiocyanate (FITC) dextran 4 kDa (FD4) in Caco-2 monolayers. Confocal analysis of monolayers showed that FD4 was localized at the paracellular space, and that there was disruption of filamentous actin, a scaffolding protein that holds tight junctions in place, Ocular drug delivery can broadly be considered in terms of topical, peri-ocular, or intra-ocular administration. The most common route of administration is topical delivery where medicaments are directly applied to the cornea, sclera and conjunctiva for local or regional actions. Delivery to peri-ocular or intra-ocular targets via either the cornea or blood retinal barrier is difficult even for highly permeable actives. The cornea is a widely accessible epithelial surface, although drug transport across this barrier is arguably more challenging than via other epithelia, Nasal administration is among the most successful approaches for the systemic delivery of macromolecules. A number of small peptides are marketed in intranasal formulations, application of bioenhancers in buccal, nasal, oral and pulmonary routes of administration, and provides information on source, model of action, test delivery model and payloads, oral and nasal routes, and to a lesser extent via pulmonary, buccal, ocular and vaginal routes

Author: Na, K.; Lkhagva-Yondon, E.; Kim, M.; Lim, Y.R.; Shin, E.; Lee, C.K.; Jeon, M.S.

Atopic dermatitis (AD) is a chronic inflammatory skin disease, dry itchy skin that results from defects in the epidermal barrier function. Aloe vera is used widely to promote general health and is administered topically to treat skin conditions such as eczema, burns and wounds, oral administration of processed A vera gel (PAG) containing low molecular weight Aloe polysaccharides to treat ovalbumin (OVA)-induced Atopic dermatitis in mice. Oral administration of PAG suppressed total and OVA-specific IgE production in sera and decreased the epidermal thickness of skin, oral administration of polysaccharides Aloe vera Gel ameliorated Atopic dermatitis , normalized tight junction gene expression and suppressed inflammatory cytokines in Atopic dermatitis skin, Atopic dermatitis (AD) is a chronic inflammatory skin disorder that results from defects in the epidermal barrier and immune dysfunction, complex pathophysiology of Atopic dermatitis is known to include genetic risk factors, environmental triggers and dysregulation of innate and adaptive immunity, Current understanding of the aetiology of AD is that disruption of the epidermal barrier leads to increased permeability of the epidermis, pathological skin inflammation and percutaneous sensitization to allergens, One of the therapeutic approaches aims to maintain or improve epidermal barrier function to ameliorate AD. The skin is composed of two barrier structures, the stratum corneum (SC) and tight junctions (TJs) that provide a physical barrier against dehydration and environmental challenges, Aloe vera has been used both as a therapeutic and dietary health supplement in the treatment of various diseases, It is known to have immunoregulatory and skin moisturizing properties, notably, A vera polysaccharides have been shown to modulate immunity in both humans and mice, topical application of polysaccharides Aloe vera gel extract helped treat the AD, It is not only used topically, but also has been administered orally via liquid formulations, tablets and capsules, however, the effects of orally administered Aloe polysaccharides in Atopic dermatitis AD-related diseases have not been fully elucidated, the average molecular weight of native polysaccharides in A vera gel is 2000 kDa or higher. We used polysaccharides Aloe vera gel (PAG), which has polysaccharides sized 5-400 kDa , polysaccharides Aloe vera gel can enhance the immunomodulatory activity of the polysaccharide, oral administration polysaccharides Aloe vera gel in ovalbumin (OVA)-induced AD mouse model and investigated how these molecules affect skin barrier function, including the genes encoding the tight junction proteins TJP-1, claudin-1 and claudin-8, and cytokines that include IL-4 and IL-17A,

Author Pooja Jain, Mohamad Taleuzzaman, Chandra Kala, Dipak Kumar Gupta

develop the phytosomal gel of aloe vera extract for improved topical delivery. Aloe vera extract loaded phytosomal system was developed by fixing the amount of aloe vera extract and ethanol and by varying the concentration of lecithin, developed formulations were evaluated for vesicular size, entrapment efficiency, PDI, zeta potential and in-vitro release. Drug release kinetics from the phytosomes follows Higuchi model. TEM micrograph confirms the uniform structure of phytosomes. Phytosomal gel of optimized phytosomal formulation (F09) was developed with 1% Carbopol 934 and physically characterized based on pH, viscosity, homogeneity and drug content. Ex-vivo permeation study showed the better permeation and flux profile of phytosomal gel with the conventional aloe vera extract gel. Also, studies on phytosomal formulation and gel showed stability up-to 3?months. Thus overall, it can be concluded that the phytosomal gel is a good carrier for topical delivery of herbal extract such as aloe vera.

Author Saeedeh Darzi Kallyanashis Paul ,Shanilka Leitan ,Jerome A. Werkmeister and Shayanti Mukherjee

Aloe vera (AV), a succulent plant belonging to the Liliaceae family, has been widely used for biomedical and pharmaceutical application. Its popularity stems from several of its bioactive components that have anti-oxidant, anti-microbial, anti-inflammatory and even immunomodulatory effects. Given such unique multi-modal biological impact, Aloe Vera has been considered as a biomaterial for regenerative medicine and tissue engineering applications, where tissue repair and neo-angiogenesis are vital, scientific evidence that demonstrates the advantage of Aloe Vera as tissue engineering scaffolds, biomaterials, regenerative medicine, foreign body response, macromolecules, anti-inflammatory material, bioink, tissue engineering

Author Mudhi AlAli , Maream Alqubaisy 1, Mariam Nasser Aljaafari , Asma Obaid AlAli , Laila Baqais , Aidin Molouki , Aisha Abushelaibi, Kok-Song Lai, Swee-Hua Erin Lim

Nutraceuticals are essential food constituents that provide nutritional benefits as well as medicinal effects, Nutraceuticals can be categorized into different classes based on their nature and mode of action, different classifications of nutraceuticals and their potential therapeutic activity, Nutraceuticals are known as bioactive substances that are present in common food or botanical-based sources, dietary supplements or functional food, supplying beneficial effects in addition to the nutritional essential components, antioxidants, phytochemicals, fatty acids, amino acids, and probiotics, nutraceuticals are well-known for their role of being involved in disease treatment and prevention, anti-aging properties, and malignancy prevention, probiotics is encouraged due to its significant role in the treatment and prevention of gastroenterological diseases, enhancing the infection response mechanism, boosting immunomodulatory activity, and contributing to reducing the impacts of autoimmune disorders and hypersensitivity, Nutraceuticals have also been shown to exert lipid-lowering, anti-inflammatory, anti-cancer and antioxidant activity, immune system is divided into two subsystems, commonly known as innate and the adaptive immune systems, subsystems involve humoral and cellular responses, vitamin C in improving the immune system by supporting the innate and adaptive systems, augmenting defense mechanisms such as phagocytosis and chemotaxis, as well as possessing antioxidant properties, provide a neutralizing effect and protection against any harm that the body might encounter, effective properties in the immune system, safety, bioactivity, and bioavailability perspective, Nutraceuticals have been classified based on their application into traditional, non-traditional, fortified, recombinant, phytochemical, herbal, functional foods, dietary supplements, probiotics and prebiotics, nutraceuticals with their beneficial effects to health, chemical constituents and functions in delivering health benefits, nature and mode of action, Functional foods are foods with benefits in health improvement and disease prevention other than only providing nutrients, dietary supplements are products that can be taken as a dietary ingredient by individuals to maintain and improve health and not to cure diseases, Probiotics are microbes that are beneficial to health and used in food, especially in milk products, promote health by providing immunologic and digestive properties, probiotic used that will survive in the human gut, prebiotics are ingredients consisting of short chain carbohydrates that improve the probiotics’ activity, prebiotics are literally fertilizing agents for probiotics that are not affected by gastric pH and stomach acids, Prebiotics are non-digestible ingredients that promote the growth of productive microorganism and affect the composition and activity of gut microbiota, These supplements are found in various forms, such as tablets, liquid-based, capsules, powder, and concentrated with specific doses, Fortified Nutraceuticals Fortified nutraceuticals such as orange juice with calcium added, or milk with cholecalciferol vitamin are foods that contain additional micronutrients or vitamins added to them to improve their value, supply the body with important nutrients that can prevent anemia and improve health, Recombinant nutraceuticals are foods that are produced by both genetic recombination and biotechnology, recombinant gene that increases ascorbic acid levels, carotenoid, and lutein to enhance immune function, nutraceuticals enhance human health and increase life expectancy along with many other processes that delay aging and prevent chronic diseases, nutraceutical supplements have shown a positive impact on cardiovascular disease, cancer, diabetes, obesity, osteoporosis and immune functions, nutraceutical modes of action take place to increase functional components which will lead to health enhancement, prebiotics and probiotics are believed to be of benefit in promoting human health, specifically in the gastrointestinal tract, most important features of nutraceuticals are their cost effectiveness, broad safety profiles both in humans and animals, tolerability, and easy availability, pharmacokinetic behavior of every drug is extremely important for the understanding of safety profile (toxico-kinetics), onset of action, required dose, and dose frequency, interactions with other drugs as well as nutrients/foods are another vital aspect of safety evaluations of nutraceuticals that assess the effect of interactions on safety, efficacy, half-life and subsequent therapeutic response, nutraceuticals are included in the dietary supplements,

Author Ruixuan Geng, Seong-Gook Kang, and Tao Tong

Skin photoaging is mainly induced by ultraviolet (UV) irradiation and its manifestations include dry skin, coarse wrinkle, irregular pigmentation, and loss of skin elasticity, Dietary supplementation of nutraceuticals with therapeutic and preventive effects against skin photoaging, cellular and molecular mechanisms of UV-induced skin photoaging, Matrix metalloproteinases, transforming growth factors, skin adipose tissue, inflammation, oxidative stress, nuclear and mitochondrial DNA, telomeres, microRNA, advanced glycation end products, the hypothalamic–pituitary–adrenal axis, and transient receptor potential cation channel V are key regulators that drive the photoaging-associated changes in skin, skin photoaging, dietary components to alleviate skin photoaging include the maintenance of skin moisture and extracellular matrix content, regulation of specific signaling pathways involved in the synthesis and degradation of the extracellular matrix, and antioxidant capacity, ingestion of food-derived functional components could be an attractive strategy to prevent skin photoaging damage, Skin aging includes natural aging, heat aging, and photoaging, photoaging is the most crucial factor causing skin aging damage. Skin photoaging is caused by long-term exposure to ultraviolet (UV) and manifests as rough, dry, and sagging skin, deeper skin wrinkles, excessive skin pigmentation, or angiotelectasis, even leading to various benign or malignant tumors, such as solar keratosis, squamous cell carcinoma, and malignant melanoma , UV activates or inhibits various signal pathways in the dermis and epidermis, leading to a decrease in the content of the extracellular matrix (ECM) and causing uneven structure or even skin collapse, methods to prevent or treat skin photoaging mainly include physical means of photoprotection (sunglasses, window films, clothing, etc.), topical treatment of active ingredients, and medical cosmetology,recently, there has been a growing awareness of the role of nutrition in skin health and specific dietary components have emerged as an effective alternative strategy to prevent and alleviate the symptoms of photoaging, dietary supplementation of functional components can protect skin from photoaging damage. Phytochemicals , functional proteins [9] and peptides , functional sugars, functional oils , probiotics , vitamins , and minerals are well-known to improve the photoaging-associated morphological abnormalities and functional decline, skin is in direct contact with the external environment and has the functions of feeling external stimuli, regulating body temperature, excreting skin metabolites, and protecting the body from physical, mechanical, and chemical damage and invasion by pathogenic microorganisms, skin consists of three parts: stratified epidermis, dermis, and subcutaneous tissue , epidermis is composed of keratinocytes (90–95% of skin cells), Langerhans cells (2%), melanocytes (3%), and Merkel cells (0.5%), epidermis contains the stratum corneum, hyaline layer, granular layer, and germinal layer, from the shallowest to the deepest, stratum corneum is the key to maintaining optimal skin hydration, cells in the germinal layer continue to proliferate and migrate to the upper layer to supply the constantly shedding stratum corneum, germinal layer contains melanocytes that can produce melanin and the content of melanin is one of the factors that determines skin color, dermis is made up of connective tissue and also contains appendages including sweat glands, sebaceous glands, blood vessels, and nerves, dermis is divided into the papillary layer and reticular layer, and there is no obvious boundary between the two layers. The thickness of the dermis is around 0.07–0.12 mm; the dermis of the palms and soles is thicker (~1.4 mm); the eyelids and tympanic membrane are thinner (~0.05 mm), papillary layer is connected to the germinal layer of the epidermis, and the reticular layer is combined with the subcutaneous tissue, main cell types in the dermis is fibroblasts, which play a vital role in skin aging ,fibroblasts synthesize and secrete ECM, including collagen, hyaluronic acid (HA), and elastin, collagen is the most important ECM in the dermis of the skin, loss of collagen will directly lead to skin sagging, aging, and decreased elasticity, HA is synthesized at the plasma membrane by HA synthases 1–3 and is known to play a key role in wound healing and tissue repair processes due to its ability to maintain a humid environment, in the dermal fibroblasts, HA synthase 2 seems to be the major isoform, elastin is the main component of elastic fibers in matrix tissue and provides resilience and elasticity to tissues and organ, reticular layer contains collagen fibers, elastic fibers, and reticular fibers, which interweave into a net to create elasticity and toughness in the skin, existing evidence suggests that damage to macromolecules present in the dermal ECM is indeed associated with skin aging, subcutaneous tissue is composed of loose connective tissue and fat lobules, and it connects the dermis with the fascia, aponeurosis, or periosteum, It can buffer mechanical pressure, store energy, and maintain body temperature, moderate amount of UV radiation can kill microorganisms, regulate the nerves, endocrine, digestion, breathing, immune system, and promote the synthesis of vitamin D. However, exposure to chronic low-dose or instant high-dose UV radiation causes harm to the eyes, skin, and immune system and is associated with the clinical hallmarks of skin aging, photoaging is mainly caused by UVA and UVB. UVA has a strong ability to induce free radicals and lipid peroxidation in cells and undermines collagen fibers and elastic fibers in the dermal tissue, impact of UVA can reach the deep layer of the dermis due to its greater penetration ability, UVA has no direct effect on DNA damage, it can generate reactive oxygen species (ROS), leading to DNA oxidative damage indirectly, UVB chiefly leads to lesions in the epidermis and superficial dermis and could be absorbed by proteins and DNA in cells, causing cell damage and mutation, 80% of facial skin aging is caused by exposure to UV , macroscopic characteristics of skin photoaging include wrinkle formation, rough texture, pigmentation, and loss of skin elasticity, histological and ultrastructural studies have shown epidermal hyperplasia, damage, and disorder of collagen fibers, and a large accumulation of abnormal elastic substances in connective tissue in photoaged skin ,these effects are less pronounced in the epidermis owing to high turnover, in contrast, the dermal region is more susceptible to photodamage, which results in loss of skin resilience, mechanisms of photoaging, Matrix Metalloproteinases, TGF (Transforming Growth Factor)-?, TGF-? is a type of cytokine that regulates cell growth and differentiation and performs a central role in the inflammatory response, tissue repair, embryonic development, and the immune response, Reduction of Skin Adipose Tissue, Inflammation and Immune Disorders, Oxidative Stress, ROS, such as superoxide ions, H2O2, and hydroxyl radicals, are chemically active and oxidize unsaturated fatty acids from cell phospholipid molecules to malondialdehyde, directly hurting functional macromolecules such as biofilms and proteins , UV radiation induces the production of ROS, which breaks the dynamic balance between oxidation and antioxidant systems in the skin and reduces its ability to remove ROS, Nuclear DNA and mtDNA Damage, UV radiation can directly or indirectly hurt DNA, Mitochondrion is the main organelle involved in skin photoaging, close connection between mitochondria and skin health, the strategy of focusing on mitochondria as a therapeutic target to boost skin health has attracted the attention of clinicians and estheticians. A great quantity of bioactive compounds have been confirmed to ameliorate mitochondrial function and have positive effects on aging and diseased skin, Telomere Shortening, Telomeres are critical structures at the end of eukaryotic chromosomes made up of numerous copies of G-rich repeats. Without telomeres, chromosomes will fuse and genetic instability will occur , MicroRNA (miRNA), regulates the senescence of human skin fibroblasts, Accumulation of Advanced Glycation End Products (AGEs), prominent feature of aging at the molecular level is the gradual accumulation of proteins that have undergone non-enzymatic modification, one of the commonest of which is glycation, Gut Microbes, gut and skin, densely vascularized and richly innervated organs with crucial immune and neuroendocrine roles, are uniquely related in purpose and function, as our primary interface with the external environment, both organs are essential to the maintenance of physiologic homeostasis, gut microbiome is the major regulator of the gut–skin axis, oral probiotics may counteract UV damage and relieve inflammatory dermatoses by regulating immune-related signal pathways, gut dysbiosis has been observed in conditions such as atopic dermatitis, mechanisms by which intestinal microbiota exert their influence on skin homeostasis appear to be related to the modulatory effect of gut microbes on systemic immunity, Activation of Hypothalamic–Pituitary–Adrenal (HPA) Axis, HPA axis is associated with the activation of a wide range of responses involving the endocrine, nervous, and immune systems, collectively known as the stress responses, Skin has neuroendocrine capabilities that also encompass all elements of the HPA axis, Transient Receptor Potential Cation Channel V (TRPV), The TRP ion channel is a type of channel protein widely distributed in the peripheral and central nervous system. TRP allows cations to pass through the cell membrane non-selectively and is responsible for various sensory responses, including heat, cold, pain, stress, vision, and taste, Efficacy and Mechanisms of Dietary Components in Mitigating Skin Photoaging: Animal and Human Evidence, oral supplementation with aloe vera polysaccharides improve skin moisture and elasticity and relieve wrinkles and roughness in eye skin

Author: Fox, L.; Gerber, M.; Du Preez, J.L.; Du Plessis, J.; Hamman, J.H.

in-vitro permeation enhancement effects of the gel and whole-leaf materials of Aloe vera using ketoprofen as a marker compound, transdermal route of drug administration offers many advantages, such as avoiding first-pass metabolism, needing less frequent dosing regimens as they produce release for long periods of time, availability of a relatively large surface area for absorption and increased patient acceptability because of its non-invasiveness, however, the outermost layer of the skin, the stratum corneum (SC), offers a formidable physical barrier to molecular transport, this layer is very specific with regards to the type of molecule that can be transported across the skin and therefore only molecules with certain physicochemical properties can readily cross the skin, this limits the range of potential drugs that can be administered trans dermally, which emphasizes the need for formulations to incorporate penetration enhancers to assist in the effective delivery of a larger variety of drugs across the skin, Penetration enhancers can be used to enhance the penetration rate of drugs across the skin by means of two possible mechanisms of action, firstly, the penetration enhancer can work by altering the solubility properties of the skin, thereby increasing the solubility of the drug within the SC; secondly, the enhancer disrupts the ordered nature of the skin lipids, which consequently influences diffusion across the SC, the use of natural products as effective and safe drug permeation enhancers is receiving considerable attention.[8] One such a natural product, Aloe vera (Aloe barbadensis Miller) juice, has shown potential to enhance the permeation of certain drug molecules through porcine ear skin membranes, mucilaginous gel of the aloe, consisting mainly of polysaccharides, holds the secret to some of the medicinal properties and biological effects of this family of plants, which was confirmed for drug absorption enhancement across intestinal epithelial cells, Membrane release studies were performed before the skin diffusion studies to determine what concentration (3.00%, 1.50% or 0.75% (w/v)) of aloe leaf materials should be used for the ketoprofen skin diffusion studies. Non-linear curve fitting was used to calculate ? and ? values as well as permeation coefficient (kp) values to give an indication of the mechanism of ketoprofen permeation enhancement across the skin by the aloe leaf materials, in-vitro skin permeation enhancement potential of Aloe Vera Gel juice was investigated by employing porcine ear skin membranes and saturated solutions of various model drugs (i.e. ‘within-vehicle’) with different molecular weights and lipophilicities (i.e. caffeine, colchicine, mefenamic acid, oxybutynin and quinine). No link was found between the lipophilicity of the drug and the permeation enhancement effect of the Aloe Vera Gel juice; however, it had a higher skin permeation enhancement effect on drugs with a higher molecular weight, mechanism was proposed whereby the smaller molecules were less efficient at blocking Aloe Vera Gel constituents from the permeation pathways, leading to a reduced opportunity for the drug to interact with the enhancing factor, which was ‘lost’ from the solution because of its permeation. In contrast, a drug with a larger molecular weight effectively blocked the permeation routes, allowing increased possibility for the drug to interact with the enhancing factor and complex with it before being transported across the skin, that is, permeation enhancement occurs by a ‘pull effect’, skin penetration enhancement of drugs by the ‘pull’ effect, whereby the permeation of the enhancer facilitates the permeation of the solute via a solvation or complexation interaction, study clearly showed a significant permeation-enhancing effect by Aloe Vera Gel gel when ketoprofen was incorporated into the solution (i.e. ‘within vehicle’), Therefore, it can be hypothesized that ketoprofen had the opportunity to interact with the aloe phytochemicals (i.e. enhancing factor) in the aloe-containing solutions to facilitate its transport across the skin.

Author: Marina González-Larena, G. García-Llatas, G. Clemente, R. Barberá, M. J. Lagarda

plant sterol (PS)-enriched beverages, milk based fruit juice (MFJPS), fruit juice (FJPS) and milk beverage (MPS), phytosterol oxidation products,

Author: Balaji Srinivasan, Aditya Reddy Kolli, Mandy Brigitte Esch, James J. Hickman

Transepithelial/transendothelial electrical resistance (TEER) is a widely accepted quantitative technique to measure the integrity of tight junction dynamics in cell culture models of endothelial and epithelial monolayers. TEER values are strong indicators of the integrity of the cellular barriers before they are evaluated for transport of drugs or chemicals. TEER measurements can be performed in real time without cell damage and generally are based on measuring ohmic resistance or measuring impedance across a wide spectrum of frequencies, some of the barrier models that have been widely characterized using TEER include the blood-brain barrier (BBB), gastrointestinal (GI) tract, and pulmonary models. Variations in these values can arise due to factors such as temperature, medium formulation, and passage number of cells, enable the transport of therapeutic drugs across these barriers in order to reach the target tissue.

Author: Panahi Y, Khedmat H, Valizadegan G, Mohtashami R, Sahebkar A.

use of Aloe vera (A. vera) for the treatment of gastroesophageal reflux disease (GERD) symptoms and compare its effects with those of omeprazole and ranitidine, Aloe vera is safe and well tolerated and reduced the frequencies of all the assessed GERD symptoms, with no adverse events requiring withdrawal, Gastroesophageal Reflux Disease (GERD) is introduced as a result of lower esophageal sphincter weakness, which returns contents of the stomach to the esophagus. Aloe vera (Aloe barbadensis) gel is known as a healing agent for the treatment of internal and external ailments. Modern research has confirmed potential therapeutic effects of A. vera gel for GERD, but there is no review study to evaluate the efficacy of A. vera gel.

Author: W. Gerber, J. D. Steyn, A. F. Kotzé, J. Hamman

Simultaneous oral intake of herbs, supplements, foods and drugs with other drug(s) may result in pharmacokinetic or pharmacodynamic interactions with the latter, pharmacokinetic interactions include the improvement of the bioavailability of a drug (i.e., by enhancing absorption and/or inhibiting metabolism) or prolongation of a drug’s plasma level within its therapeutic window (i.e., by decreasing excretion), whereas beneficial pharmacodynamic interactions include additive or synergistic effects, Mechanisms by which pharmacokinetic interactions can cause beneficial effects include enhancement of membrane permeation (e.g., structural changes in the epithelial cell membranes or opening of tight junctions), modulation of carrier proteins (e.g., inhibition of efflux transporters and stimulation of uptake transporters) and inhibition of metabolic enzymes, delivering drugs that are poorly bioavailable in therapeutic levels via alternative routes of administration than parenteral injection, bioavailability, efflux inhibition, pharmacokinetic interactions, tight junction modulation, enzyme inhibition, patients are taking food, herbs, supplements and/or over-the-counter health products together with their prescribed medications, concomitant use of these products may lead to food-drug, herb-drug, supplement-drug and/or drug-drug interactions, Pharmacodynamic interactions mainly involve diverse reactions at receptor sites resulting in antagonistic or synergistic effects as well as causing changes in physiological environments, while pharmacokinetic interactions affect the absorption, distribution, metabolism and excretion of the co-administered agent (e.g., food component, herb, supplement, health product ingredient) and/or co-administered drug, drugs present with poor oral bioavailability include low solubility, extensive pre-systemic metabolism, poor membrane permeability and active efflux transportation, Deliberate inhibition of pre-systemic metabolism or efflux can achieve improved bioavailability and prolonged half-lives of poorly bioavailable drugs with consequently less frequent dosing and a lower total required dose (i.e., inhibition of P-glycoprotein [P-gp], cytochrome P450 [CYP450] and organic anion transporters, in vitro drug absorption enhancing effects of Aloe Vera Gel gel and whole leaf materials were first shown across intestinal epithelial cell (Caco-2) monolayers, which was attributed to opening of tight junctions between adjacent epithelial cells as indicated by a reduction in trans-epithelial electrical resistance. Other publications also reported the ability of aloe materials to increase intestinal membrane permeation of various drugs in vitro, aloe materials were incorporated into solid oral dosage forms (i.e., dual phase spherical bead system), Aloe vera liquid preparations could increase the bioavailability of vitamins in humans when co-administered, Aloe Vera Gel gel could also increase the buccal absorption of the anti-retroviral drug, didanosine, by as much as 11-fold, mechanism responsible for the absorption enhancing effects may be because of increased residence time due to muco-adhesive abilities of aloe gel or that the polysaccharides in aloe are able to weaken the epithelial barrier by dismantling intercellular junctions, aloe vera potential modulation of cimetidine efflux, Aloe vera gel shown to improve ketoprofen diffusion across dermatomed skin, Aloe vera gel polysaccharides inhibit indinavir metabolism in an in vitro LS180 cell model, dietary supplement is defined as oral ingested product that is intended to supplement a person’s diet and is not necessarily considered food (e.g., vitamins, minerals, herbs, amino acids), Understanding dietary supplement-drug interactions is especially important as a relatively large number (about 25%) of individuals that make use of dietary supplements on a regular basis, take it with one or more prescription drugs, pharmacokinetic interactions are discussed within the broad categories of food-drug, herb-drug, dietary supplement-drug and drug-drug interactions, Inhibition of efflux transporters and metabolism enzymes by co-administered compounds may lead to increased bioavailability of drugs with poor pharmacokinetic properties. Some of these interactions can potentially be coordinated by including functional excipients (i.e., compound that causes beneficial interaction) with the drug in a dosage form. This technique may even be used to lower the quantity of active drug required per administered dose due to increased bioavailability,

Author: Haasbroek A1, Willers C2, Glyn M3, du Plessis L4, Hamman J5.

absorption enhancing agents, macromolecular drugs (e.g., protein and peptide drugs), oral bioavailability, Absorption-enhancing agents of natural origins, green chemistry, enhance drug permeation across the intestinal epithelial barrier, a clear decrease in transepithelial electrical resistance (TEER) of Caco-2 cell monolayers exposed to A. vera gel, open tight junctions between the epithelial cells, evia the paracellular or transcellular pathways pithelial cell monolayers, harsh gastrointestinal environment where enzymatic and chemical activity, through the tight junctions and intercellular spaces cause extensive degradation, especially, of protein and peptide drugs , co-administration of absorption enhancers, adherence junctions, movement of the drug molecules across the intestinal epithelium, functional excipients, decreasing mucus viscosity, changing membrane fluidity, disrupting the structural integrity of the intestinal wall or modulating the tight junctions, derived from plants (capsaicin, piperine, quercetin, and Aloe vera), regulation of gastrointestinal function, enzyme inhibition, P-gp efflux inhibition, mucoadhesion, and tight junction modulation, acetylated mannan (acemannan or aloverose), across intestinal epithelial cell monolayers, excised intestinal tissues, TEER reduction, transport enhancement of the FD-4, accumulation of FD-4 between the epithelial cells (i.e., in the intercellular spaces), and F-actin disruption

Author T Lebitsa, A Viljoen, Z Lu, J Hamman – Current drug delivery, 2012

increase the bioavailability of vitamins, enhance the in vitro transport of a macromolecular drug across intestinal epithelial cell monolayers, transepithelial electrical resistance and permeability of atenolol across excised intestinal tissue, transport of FITC-dextran across Caco-2 cell monolayers, ability to statistically significantly reduce the transepithelial electrical resistance of excised intestinal tissue, act as drug absorption enhancing agents across intestinal epithelia

Author Panahi Y, Sharif MR, Sharif A, Beiraghdar F, Zahiri Z, Amirchoopani G, et al.

Diaper dermatitis (DD) is a common inflammatory disorder among children and infants, It refers to any acute inflammatory skin eruption that occurs in area covered by diaper and caused by either direct effect of wearing diapers or as a result of increased skin pH, zinc deficiency, prolonged exposure to moisture, and irritants like urine and feces. The combination of these factors leads to overhydration of the stratum corneum as well as chemical and mechanical abrasion, which compromises barrier function and makes the stratum corneum more susceptible to frictional trauma and the penetration of irritants and microbes. In addition, the presence of microorganisms especially Candida plays a secondary role in the development of DD [2, 6]. DD is uncommon during the first few months of life as fecal enzymes are present in low levels during this period. It usually peaks between 6 and 12 months of age and may continue till diapers are not further used in children negative side effects such as irritation, erythema, and papules, it is essential to identify effective strategies in order to decrease the prevalence of DD in children or infants, particularly if a patient does not respond to standard therapy, use of medicinal plants as antibacterial and anti-inflammatory drugs as Aloe vera and C. officinalis are two medicinal plants with diverse biological activities including anti-inflammatory and antimicrobial effects, compare the therapeutic efficacies of Aloe vera cream and Calendula officinalis ointment on the frequency and severity of Diaper dermatitis in children, topical Aloe and in particular Calendula could serve as safe and effective treatment for the treatment of diaper dermatitis in infants,

Author: E. Leucuta, Sorin

Activation-modulated DDS; Biodegradable Systems; Drug delivery systems; Enzyme Activated; Hopfenberg Model; Microreservoir Partition Controlled DDS; Osmotic Pressure Activated DDS; Polymer Matrix-diffusion DDS; medicine; modified release; pharmacy, new generations of pharmaceutical systems: medicines with extended release, controlled release pharmaceutical systems, pharmaceutical systems for the targeted delivery of drug substances. The latest advances and approaches for delivering small molecular weight drugs and other biologically active agents such as proteins and nucleic acids require novel delivery technologies, the success of a drug being many times dependent on the delivery method. All these dosage forms are qualitatively superior to medicines with immediate release, in that they ensure optimal drug concentrations depending on specific demands of different disease particularities of the body. Drug delivery of these pharmaceutical formulations has the benefit of improving product efficacy and safety, as well as patient convenience and compliance, biopharmaceutical, pharmacokinetic, pharmacologic and technological principles in the design of drug delivery systems with modified release as well as the formulation criteria of prolonged and controlled release drug delivery systems. pharmaceutical prolonged and controlled release dosage forms intended for different routes of administration: oral, ocular, transdermal, parenteral, pulmonary, mucoadhesive, but also orally fast dissolving tablets, gastroretentive drug delivery systems, colon-specific drug delivery systems, pulsatile drug delivery systems and carrier or ligand mediated transport for site specific or receptor drug targeting. Specific technologies are given on the dosage forms with modified release as well as examples of marketed products

Author Tarameshloo M, Norouzian M, Zarein-Dolab S, Dadpay M, Mohsenifar J, Gazor R.

Wound healing, a complex interaction among cells, extracellular matrix, blood vessels, proteases, cytokines, and chemokines, is still a controversial topic in surgical medicine, several complications such as delayed wound healing, superficial wound infection and post-operative/post-traumatic neuropathic chronic cutaneous pain have been reported by patients who had closed incisional wounds after the surgery, Aloe vera, an herbal plant of the lily family, has been used to treat various diseases for centuries , topical application of Aloe vera as a natural remedy, has contributed to the rapid tissue repairing process of burns, wounds, frostbite, skin infection and dermatitis, active molecules that act on fibroblasts, macrophages and epidermal cells activity, stimulate formation of epidermal tissue, increase collagen synthesis and remodeling and enhance tensile stress, thyroid hormone has been recommended as a potential wound healing agent, efficient in stimulating keratinocyte proliferation, epidermal proliferation, dermal thickening and hair growth in vitro, thyroid hormone enhances local response to growth factors and gene expression of keratins, Silver sulfadiazine (SSD) is a common anti-infective agent used to control bacterial proliferation and manage wound infection. Although indicated for deep partial-thickness and full-thickness injuries and suggested as effective in reducing inflammatory and granulation phases of healing in sutured incisions, SSD has been reported to have cytotoxic effects on fibroblasts and keratinocytes in vitro and retard wound healing in vivo , despite this, SSD is the most extensively used topical agent for the treatment of wounds effects of Aloe vera gel, thyroid hormone cream and silver sulfadiazine cream on sutured incisions in Wistar rats, 250 to 300 g, received surgical incisions followed by topical application of Aloe vera gel, thyroid hormone cream and silver sulfadiazine 1%. To assess the efficacy of each treatment technique, a histological approach was used to evaluate the mean number of fibroblasts, macrophages, neutrophils, blood vessel sections and thickness of the regenerating epithelium and dermis on days 4, 7 and 14. Re-epithelialization and angiogenesis were significantly improved in Aloe vera gel group compared with the other treatments while thyroid hormone cream had positive effects on day 4 (P?0.05), results indicated that Aloe vera was significantly more effective in wound healing as attested by tensile stress parameters in sutured incisions

Author: Hendrik J.R. Lemmer, Josias Hamman

Inclusion of absorption-enhancing agents in dosage forms is one approach to improve the bioavailability of active pharmaceutical ingredients with low membrane permeability. Tight junctions are dynamic protein structures that form a regulated barrier for movement of molecules through the intercellular spaces across the intestinal epithelium. Some drug absorption enhancers are capable of loosening tight junctions and thereby facilitate paracellular absorption of drug molecules, physiology of tight junctions as well as the mechanisms through which tight junctions can be modulated is discussed. Selected tight junction modulators are specifically described including chelating agents (e.g., ethylenediaminetetraacetic acid), cationic polymers (e.g., chitosan and derivatives), toxins (e.g., zonula occludens toxin), and plant-derived materials (e.g., Aloe vera gel), absorption enhancement, chitosan, paracellular pathway tight junction, zonula occludens toxin, As more and more drugs are developed with low membrane permeability, new interest is generated in finding ways to enhance their absorption. The progress made in comprehending the function and structure of tight junctions has contributed to advances in terms of enhanced drug delivery through the paracellular pathway. Although tight junction modulation holds great potential for effective oral delivery of poorly absorbable drugs

Author Bathini Chandrahas, A. Jayakumar, A. Naveen, K. Butchibabu, P. K. Reddy, T. Muralikrishna

efficacy of Aloe Vera mouth rinse on experimental plaque accumulation and gingivitis, Plaque control and prevention of gingivitis is the main goal of prevention of periodontal diseases.Complete plaque removal is difficult to achieve, and prevention of periodontal disease can be enhanced either by reducing the quantity of plaque below the individual’s threshold for disease or changing the quality of plaque to a more tissue-friendly composition, for effective plaque control, several mechanical oral hygiene aids as well as a number of antiplaque agents such as chlorhexidine, essential oil containing mouthrinses, and triclosan are available, chlorhexidine has shown distinct advantage and efficacy, but side effects such as staining of the teeth and the tongue, altered taste sensation, and increased calculus formation often deters its use for long periods, hence, there is a need to develop a naturally occurring, indigenous and cost-effective oral hygiene aid. One such aid could be in the form of Aloe vera extract. has anti-inflammatory properties, antiulcer activity, astringent effect, and possibility of reducing scars and enhancing wound healing, the above properties along with the ease of availability, with no known adverse effects and cost-effectiveness, make Aloe vera an ideal candidate for plaque control and thereby reduce gingivitis and probably later periodontitis, studies evaluating the effectiveness of Aloe vera incorporated in a dentifrice or as a locally applied gel showed a significant reduction of gingivitis and plaque accumulation after the use of this natural product, the purpose of this study was to assess the antiplaque and antigingivitis effect of Aloe vera in an “experimental gingivitis” model.

Author: Moncrieff G, Cork M, Lawton S, Kokiet S, Daly C, Clark C.

pathophysiology of dry-skin conditions, emollient therapy, Dry skin (xerosis) is a common symptom of a number of skin conditions, including atopic dermatitis/eczema (AD/AE), ichthyosis, irritant contact dermatitis, psoriasis and asteatotic eczema, frequent washing, use of harsh detergents and exposure to low-humidity (e.g. air-conditioned) environments, Dry skin is synonymous with a skin-barrier defect, loss of water from the stratum corneum (SC), skin barrier, prevents the penetration of harmful irritants and allergens, well-hydrated corneocytes that are enclosed within a matrix of intercellular lipids, aloe vera moisturizing, corneocytes contain natural moisturizing factor (NMF), a collection of hygroscopic compounds, which attract and hold water in the cells, natural humectants are required to maintain the skin’s plasticity and development of dehydration of the corneocytes, lipid lamellae, desquamation of the epidermal barrier, epidermal barrier structural protein filaggrin, Emollient products can be formulated with additional ingredients such as humectants, physiological lipids and antipruritic agents, Physiological lipids such as ceramides, cholesterol and free fatty acids, naturally found in the SC, replenish and restore the intercellular lipid matrix, emollient formulation, Aqueous cream, leave-on or washing product, emollient preparations

Author: Saeed Alqahtani, Loqman Mohamed, Amal Kaddoum

For orally administered drugs, their intestinal absorption and hepatic metabolism are key players for determining a drug’s systemic bioavailability and thus therapeutic effect. Drug absorption and metabolism are both complicated processes, with many physicochemical and physiological factors involved. Understanding the contribution of each of these processes is essential in regulating a drug’s level in the bloodstream and in maintaining its optimum therapeutic outcome and safety, intestine and liver as barriers to drug delivery and systemic bioavailability, characterize and predict drug intestinal absorption and hepatic

Author: B Carien, V Alvaro, H Josias

Clinically, significant herb-drug interactions have been previously documented and can be pharmacodynamic and/or pharmacokinetic in nature. Pharmacokinetic interactions have been attributed to induction or inhibition of either metabolic enzymes or efflux transporters, study identified a modulation effect of efflux transporters by certain aloe materials, herb-drug pharmacokinetic interactions when drugs that are substrates for these efflux transporters are taken simultaneously with aloe material, aloe materials may be used for drug absorption enhancement for drugs with low bioavailability due to extensive efflux, drugs crossing the intestinal epithelium membrane by passive diffusion may be substrates for efflux transporters that extrude compounds back into the gastro-intestinal lumen from within the epithelial cells, Herb-drug interactions can be pharmacodynamic or pharmacokinetic in nature and in some cases, may be clinically significant. Pharmacokinetic herb-drug interactions have been attributed to induction or inhibition of either metabolic enzymes or efflux transporters by phytoconstituents present in the herbs, Inhibition of drug efflux by co-administered herbs would result in higher uptake of the drug that may necessitate a reduction in drug dose to prevent toxic adverse effects, Aloe Vera Gel juice did not inhibit P-gp efflux transport of digoxin across Caco-2 cell monolayers, aloe vera materials on the efflux of cimetidine across excised rat intestinal tissues to identify potential interactions due to efflux modulation.

Author Mansour G, Ouda S, Shaker A, Abdallah HM.

clinical efficacy, and safety of newly customized natural oral mucoadhesive gels, containing either aloe vera or myrrh as active ingredients, in the management of minor recurrent aphthous stomatitis (MiRAS), w natural gels, containing aloe vera and myrrh, were prepared in a concentration of (0.5% w/w), in addition to a plain mucoadhesive gel used as a placebo, Aloe was superior in decreasing ulcer size, erythema, and exudation; whereas myrrh resulted in more pain reduction.

Author J. Vis. Ghaffarian, R.; Muro, S.

Sub-micrometer carriers (nanocarriers; NCs) enhance efficacy of drugs by improving solubility, stability, circulation time, targeting, and release. Additionally, traversing cellular barriers in the body is crucial for both oral delivery of therapeutic NCs into the circulation and transport from the blood into tissues, where intervention is needed. NC transport across cellular barriers is achieved by: (i) the paracellular route, via transient disruption of the junctions that interlock adjacent cells, or (ii) the transcellular route, where materials are internalized by endocytosis, transported across the cell body, and secreted at the opposite cell surface (transyctosis). Delivery across cellular barriers can be facilitated by coupling therapeutics or their carriers with targeting agents that bind specifically to cell-surface markers involved in transport, methods to measure the extent and mechanism of NC transport across a model cell barrier, which consists of a monolayer of gastrointestinal (GI) epithelial cells grown on a porous membrane located in a transwell insert. Formation of a permeability barrier is confirmed by measuring transepithelial electrical resistance (TEER), transepithelial transport of a control substance, and immunostaining of tight junctions. As an example, ~200 nm polymer NCs are used, which carry a therapeutic cargo and are coated with an antibody that targets a cell-surface determinant, Transcellular transport is determined by addressing the effect of modulating endocytosis and transcytosis pathways.

Author Alam S, Ali I, Giri KY, Gokkulakrishnan S, Natu SS, Faisal M, Agarwal A, Sharma H.

pharmacological agents include corticosteroids, enzymes, interferon-gamma, antioxidants, methylxanthine derivatives, placental extracts, immune milk, turmeric, colchicine, tea pigments, aloe vera, and spirulina, Antioxidants are believed to improve the symptoms by protecting cells from damage from free radicals. Agents such as lycopene, spirulina, turmeric, aloe vera and green tea possess antioxidant properties which are believed to aid in the relief of symptoms, aloe vera was shown to be superior to curcumin in relieving the burning sensation, Aloe vera was shown to be most effective in burning sensation relief whereas it was not as efficacious as many other agents in improving mouth opening. Aloe vera contains vitamins, enzymes, minerals, sugars, lignin, saponins, salicylic acids, and amino acids. Vitamin A, C, and E are antioxidants that can aid in scavenging free radicals, and enzymes such as bradykinase which help in reducing inflammation through topical application. It also contains polysaccharides with anticancer, anti-inflammatory, and wound-healing properties , these properties might explain the reason for its efficacy in relieving the burning sensation.

Author: Van Smeden J, Janssens M, Gooris GS, et al.

skin protects the body from unwanted influences from the environment as well as excessive water loss, barrier function of the skin is located in the stratum corneum (SC),SC consists of corneocytes embedded in a lipid matrix. This lipid matrix is crucial for the lipid skin barrier function, relation between lipid modulations and the impaired skin barrier function, relation between lipid modulations and the impaired skin barrier function, lipid composition, lipid organization and skin lipid barrier, skin consists of the epidermis and dermis as well as the subcutaneous fat tissue [1]. The epidermis is the outermost layer of the skin and consists of four distinctive layers. Each layer displays one of the sequential differentiation stages of the keratinocytes, the major cell type in the epidermis. The layers include the superficial stratum corneum (SC), stratum granulosum (SG), stratum spinosum (SS), and the inner most stratum basale (SB). The SG, SS and SB are part of the viable epidermis (thickness: 50–100 ?m), whereas the SC (thickness: 10–20 ?m) is part of the non-viable epidermis and the final differentiation product. The SB contains the proliferating keratinocytes. After the keratinocytes escape from the SB, they transiently migrate towards the SC, after which they are finally released from the skin surface, a process called desquamation. During this migration the keratinocytes differentiate: They flatten out and finally adopt the dimensions which are characteristic for the dead cells of the SC, the corneocytes, keratinocytes in the SG contain a high number of membrane-coating granules referred to as the lamellar bodies (LBs) in which lipids are stored, such as glucosylceramides (GlcCERs), sphingomyelin and phospholipids, these are precursors of the SC lipids, and are enzymatically processed into their final constituents: ceramides (CERs) and free fatty acids (FFAs), CERs and FFAs are, together with cholesterol (CHOL), the main lipid classes in the SC. By means of exocytose, the lipid content of the LBs is released together with hydrolytic enzymes into the intercellular space at the SG/SC interface, human SC contains 10 to 25 corneocyte layers that are oriented approximately parallel to the skin surface and are embedded in a lipid matrix , structure of the SC is often referred to as a “bricks in mortar” structure, in which the corneocytes are the bricks and the lipids are the mortar, corneocytes are filled with water and microfibrillar keratin that is surrounded by a cornified envelope which consists of a densely crosslinked layer of proteins such as filaggrin, loricrin and involucrin , monolayer of non-polar lipids (?-hydroxylated CERs and FFAs) referred to as the lipid envelope is esterified to the cornified envelope, mainly to glutamate residues of involucrin, lipid envelope is suggested to form a template for the formation of the intercellular lipid layers , cornified envelope, together with the lipid envelope, minimizes the uptake of most substances into the corneocytes and allows proper formation of the lipid matrix. Indeed, a deficient lipid envelope results in a defective skin permeability function and an irregular lipid matrix, lipid matrix acts as the main barrier for diffusion of substances through the skin

Authors: N Ranade, Arati; S. Ranpise, Nisharani; Ramesh, C.

Approach of novel drug delivery system (NDDS) overcomes the limitations of conventional dosage forms, delivery of herbal drugs , need to amalgamate the concept of NDDS in delivery of herbal constituents, deliver and retain two herbal constituents in stomach for better action against Helicobacter pylori induced gastric ulcers. The objective was to develop a bilayer floating tablet of ellagic acid and Aloe vera gel powder through rational combination of excipients to give the lowest possible lag time with maximum drug release in the period of 4 h. Formulation F9 containing 100 mg of HPMC K15M, 27 mg of crospovidone, 80 mg of mannitol and effervescent agents in the ratio 1:2 gave 92% drug release and desired floating properties. In vivo studies showed that combination of ellagic acid and Aloe vera gave 75 % ulcer inhibition in comparison to 57% ulcer inhibition in the group which was administered with ellagic acid alone. This suggests the use of bilayer floating tablet in gastric ulcer treatment, floating; gastric ulcer; optimization

Author Vandana, K.R.; Yalavarthi, P.R.; Sundaresan, C.R.; Sriramaneni, R.N.; Vadlamudi, H.C.

Drug loading capacity, flux, in-vitro permeation, paws edema, percentage inhibition, stability, nimesulide emulsion for incorporation in Aloe vera gel base to formulate ‘nimesulide – Aloe vera transemulgel, anti-inflammatory studies, use of nimesulide is banned for oral administration, due to its potential for inducing hepatotoxicity and thrombocytopenia, the use of nimesulide for topical delivery is prominent in the treatment of many inflammatory conditions including rheumatoid arthritis. The drug loading capacity of transdermal gels is low for hydrophobic drugs such as nimesulide. Nimesulide can be effectively incorporated into emulgels (a combination of emulsion and gel). Aloe vera has a mild anti-inflammatory effect and in the present study Aloe vera gel was formulated and used as a gel base to prepare Aloe vera transemulgel, the emulgels thus prepared were evaluated for viscosity, pH, in-vitro permeation, stability and skin irritation test. In-vivo anti-inflammatory studies were performed using carrageenan induced hind paw edema method in Wistar rats, effective permeation of nimesulide from Aloe vera transemulgel (53.04 %) was observed compared to CNG (44.72 %) at 30 min indicating better drug release from Aloe vera transemulgel. Topical application of the emulgel found no skin irritation. Stability studies proved the integrity of the formulation. The percentage of inhibition of edema was highest for the prepared Aloe vera transemulgel (67.4 % inhibition after 240 min) compared to CNG (59.6 %). From our results, it was concluded that the Aloe vera gel acts as an effective gel base to prepare nimesulide emulgel with high drug loading capacity (86.4 % drug content) compared to CNG (70.5 % drug content) with significant anti-inflammatory effect.

Author Pereira GG, Guterres SS, Balducci AG, Colombo P, Sonvico F

Burns are serious traumas related to skin damage, causing extreme pain and possibly death, Natural drugs such as Aloe vera and vitamin E have been demonstrated to be beneficial in formulations for wound healing. The aim of this work is to develop and evaluate polymeric films containing Aloe vera and vitamin E to treat wounds caused by burns. Polymeric films containing different quantities of sodium alginate and polyvinyl alcohol (PVA) were characterized for their mechanical properties and drug release, bioadhesive films containing vitamin E acetate and Aloe vera could be an innovative therapeutic system for the treatment of burns, in addition to pain and distress, a large burned area will leave the patient with visible physical scars and invisible psychological sequelae, concerning skin damage, the treatment of burns is complex and painful and requires the use of several drugs administered separately or combined, The dressings are a form of treatment of skin wounds aimed at favoring and supporting the healing process, Potential vectors for the controlled release of substances for the treatment of skin damage occurring in wounds and burns are polymeric films. Thin films have been extensively used around the world for tissue repair and closure of wounds, Polymeric film offers advantages over other pharmaceutical forms, such as liquid or semisolid drug delivery products, as it provides a large surface area of application, adhesion to the damaged tissue, and absorption of exudates, the use of natural polymers is supported by their many desirable properties, such as biocompatibility, low irritancy, and lack of toxicity , as in the case of polysaccharides. In addition, wound dressings are in some cases able to prevent loss of body fluid, prevent exudates build up [9], protect the wounds from external contamination, provide sufficient bactericidal effects to inhibit infection , and prepare an optimum wound bed for autographing, To reduce pain and accelerate the healing process, many natural substances have been traditionally used and more recently have been scientifically studied as Aloe vera has been used in a host of curative purposes including treatment of skin disorders and healing of wounds, potent moisturizing agent, it helps in the healing process of skin lesions and alleviates pain, develop and characterize a polymeric film containing Aloe vera and vitamin E acetate with the aim of providing an innovative system for burn wound treatment. The two polysaccharides selected to produce the film were hyaluronic acid and sodium alginate, Bioadhesive polymeric films loaded with vitamin E acetate and Aloe vera were produced and tested on the intact skin of healthy volunteers. The films showed mechanical resistance and flexibility suitable for application in burn wounds. The release profile obtained from the film showed a biphasic controlled release of vitamin E acetate for more than 12 hours. The tape stripping on intact skin showed that the polymeric film formulation facilitates a deeper accumulation of the vitamin E acetate in the stratum corneum when compared to a traditional semisolid formulation The polymer film formulation containing hyaluronate and alginate appears to be a promising approach for the application of substances able to reduce damage and facilitate the healing process, Aloe vera extracts and the antioxidant vitamin E acetate.

Author ULBRICHT CATHERINE ET AL

Alopecia (hair loss), Alzheimer’s disease, antioxidant, arthritis (osteoarthritis and rheumatoid arthritis), asthma, bacterial skin infections, candida skin infections, chronic fatigue syndrome, chronic leg ulcers, congestive heart failure, corneal abrasions/ulcers, coronary artery disease prevention, diabetic ulcers, duodenal ulcer, dry skin (aloe gel gloves), frostbite, functional bowel disorders, gastric acid reduction (hyperacidity), gastric ulcer, helminthic infections, hepatitis, human papilloma virus hyperlipidemia, in?ammatory bowel disease, lichen planus, Parkin-son’s disease, peptic ulcer, periodontal surgical rinse, post dermabrasion wound healing, radioprotection, sunburn, systemic lupus erythematosus, tic douloureux, untreatable advanced solid neoplasms, urolithiasis (bladder stones), Aloe Vera Gel gel or extract is used topically to reduce pain and in?ammation, enhance healing of skin wounds (abrasions , cuts, and ulcers), or treat psoriasis, frostbite injury, burns, infections (cold sores). Medical attention should be sought for severe burns, wounds, or frostbite, polysaccharide glucomannan is an effective human skin moisturizer, which accounts for its use in many cosmetics. Acemannan, the major carbohydrate fraction in the gel, is a water-soluble long-chain mannose polymer, modulate immune function (particularly macrophage activation and cytokine production) and to accelerate wound healing. The macrophage stimulating principle of acemannan appears to reside in the high molecular weight polysaccharides Aloeride, Acemannan has also been reported to exhibit antineoplastic and antiviral effects in vitro, anti-in?ammatory properties, enhance antibody production, aloe’s local anti-in?ammatory activity, possibly because of an inhibitory effect on the arachidonic acid pathway via cyclooxygenase, veracylglucan C exhibited signi?cant cell proliferative and anti-in?ammatory activities, free radical scavenging and other antioxidant properties, Topical aloe’s anti-in?ammatory properties do not appear to interfere with wound healing, but rather increase wound tensile strength, possibly because of the ?broblast stimulating activity of mannose-6-phosphate, Promotion of apoptosis has been reported in vitro as a possible antineoplastic mechanism, Aloe appears to affect detoxi?cation of reactive metabolites by liver and other organs, aloe polysaccharides might have a radio-protective effect on nonmalignant cells via its ability to modulate the cell cycle,

Author: Mária A.Deli

epithelial and endothelial barriers of the human body are major obstacles for drug delivery to the systemic circulation and to organs with unique environment and homeostasis, like the central nervous system. Several transport routes exist in these barriers, which potentially can be exploited for enhancing drug permeability. Beside the transcellular pathways via transporters, adsorptive and receptor-mediated transcytosis, the paracellular flux for cells and molecules is very limited, lipophilic molecules can diffuse across the cellular plasma membranes, the junctional complexes restrict or completely block the free passage of hydrophilic molecules through the paracellular clefts, Recent advances in barrier research led to the discovery of an increasing number of integral membrane, adaptor, regulator and signalling proteins in tight and adherens junctions. New tight junction modulators are under development, which can directly target tight or adherens junction proteins, the signalling pathways regulating junctional function, or tight junction associated lipid raft microdomains. Modulators acting directly on tight junctions include peptides derived from zonula occludens toxin, or Clostridium perfringens enterotoxin, peptides selected by phage display that bind to integral membrane tight junction proteins, and lipid modulators. They can reversibly increase paracellular transport and drug delivery with less toxicity than previous absorption enhancers, and have a potential to be used as pharmaceutical excipients to improve drug delivery across epithelial barriers and the blood-brain barrier.

Author: W Chen, Z Lu, A Viljoen, J Hamman Planta Medica, 2010

Aloe vera (L.) Burm. f. (Aloe barbadensis Miller) gel and whole leaf extract have effect on the permeability of Caco-2 cell monolayers, transepithelial electrical resistance, test solutions to measure reversibility of the effect, A. vera gel and whole leaf extract were able to significantly reduce the transepithelial electrical resistance of the Caco-2 cell monolayers at concentrations above 0.5?% w/v and thereby showed the ability to open tight junctions between adjacent cells. This effect was fully reversible, as the electrical resistance of the cell monolayers returned to the original value upon removal of the test solutions. The A. vera gel and whole leaf extract solutions significantly enhanced the transport of insulin across the Caco-2 cell monolayers compared with the control. The results suggest that these plant products have a high potential to be used as absorption enhancers in novel dosage forms for drugs with poor bio availabilities when administered orally. On the other hand, an uncontrolled increase in the bioavailability of drugs that are taken simultaneously with A. vera gel and whole leaf extract products may result in adverse effects,

Author: G Ital Dermatol Venereol. 2009;144(1):85–91 Feily A, Namazi MR..

Aloe vera or Aloe barbadensis, dermatology-oriented, Topical application of aloe vera, effective for genital herpes, psoriasis, human papilloma virus, seborrheic dermatitis, aphthous stomatitis, xerosis, lichen planus, frostbite, burn, wound healing and inflammation, biological vehicle and an anti-microbial and antifungal agent and also as a candidate for photodynamic therapy, Aloe Vera can help to calm sunburn, even severe burns that have begun to blister, Aloe Vera can help decrease and possibly even prevent the appearance of wrinkles

Author Jettanacheawchankit, S.; Sasithanasate, S.; Sangvanich, P.; Banlunara, W.; Thunyakitpisal, P..

Gingival fibroblasts, GF proliferation; keratinocyte growth factor-1, vascular endothelial growth factor (VEGF),and type I collagen production, acemannan, Aloe vera, proliferation, growth factor, oral wound healing, immunostimulant effect by activating macrophages

Author Charoen Choonhakarn, Ploysyne Busaracome, Bungorn Sripanidkulchai, Pongdech Sarakarn

efficacy of Aloe Vera and 0.1% triamcinolone acetonide (TA) in mild to moderate plaque psoriasis, clinical response were evaluated using the Psoriasis Area Severity Index (PASI) and the Dermatology Life Quality Index (DLQI), AV cream may be more effective than 0.1% % triamcinolone acetonide cream in reducing the clinical symptoms of psoriasis; however, both treatments have similar efficacy in improving the quality of life of patients with mild to moderate psoriasis.

Author: Makoto Takahashi, Dai Kitamoto, Yonathan Asikin, Kensaku Takara, Koji Wada

versatile skin care properties, enhance the bioavailability, interfacial and biochemical properties, liposomes, aloe vera induces proliferation and type I collagen synthesis in human fibroblasts, Type I collagen is a major structural protein and is found in large quantities in various parts of the body, especially in the skin, decrease of type I collagen induces wrinkle formation, which is a common phenomenon of aged skin, develop new formulations using Aloe vera Gel extract which enhance the skin penetration as well as the skin care properties, Liposomes have been receiving increasing attention as a drug carrier, because they are able to retain hydrophilic substances in the inner aqueous phase and hydrophobic substances in the bilayer wall, proliferation and collagen synthesis in human skin cell lines

Author M. E. Morales, V. Gallardo, B. Clares, M. B. Garcia, and M. A. Ruiz

Cellulite, a clinical syndrome mainly affecting women, involves specific changes in conjunctive dermic and subcutaneous tissue, leading to vascular and hypertrophic alterations in adipose tissues and the consequent alteration of tissue structure, design of hydrogels and pluronic-lecithin organogels elaborated as vehicles of Aloe vera (Aloe vera barbadensis miller) and Hydrocotyle asiatica (Centella asiatica) for the treatment of cellulite, hydrogels show better organoleptic characteristics than organogels, rheological point of view, both hydrogels and organogels display a plastic behavior. However, the main difference between the two is that the more complex internal structure of the organogel bestows it with more viscosity. Finally, in vitro tests with Franz-type diffusion cells revealed that the release of cosmetic active principle from the tested excipients was appropriate, both in terms of magnitude and velocity.

Author Eshghi F, Hosseinimehr SJ, RAloe Vera High Molecular Polysaccharidesani N, Khademloo M, Norozi MS, Hojati O.

Aloe vera is an herbal medicine, which has wound healing effects in burn injury. This study assessed the effects of Aloe vera cream in reducing postoperative pain, post defection pain, and its promotion of wound healing after open hemorrhoidectomy, cream containing Aloe vera versus a placebo cream on posthemorrhoidectomy pain, use of analgesics was recorded, topical aloe cream group had significantly less postoperative pain, Application of Aloe vera cream on the surgical site is effective in reducing postoperative pain both on resting and during defecation, healing time, and analgesic requirements

Author Mansourian A, Momen-Heravi F, Saheb Jamee M, Esfehani M, Khalilzadeh O, Momen Beitollahi J.

Corticosteroids are the mainstay for treatment of oral lichen planus (OLP), Triamcinolone acetonide, therapeutic effects of aloe vera (AV) mouthwash with triamcinolone acetonide 0.1% (TA) on OLP, Thongprasom index, AV mouthwash is an effective substitute for TA in the treatment of OLP.

Author A. Pradeep, E. Agarwal, S. Naik

controlled clinical trial was designed to evaluate the clinical and microbiologic effects of a commercially available dentifrice containing aloe vera on the reduction of plaque and gingival inflammation in patients with gingivitis, Toothpaste containing aloe vera showed significant improvement in gingival and plaque index scores as well as microbiologic counts compared with placebo dentifrice. These improvements were comparable to those achieved with toothpaste containing triclosan, Toothpaste containing aloe vera may be a useful herbal formulation for chemical plaque control agents and improvement in plaque and gingival status.

Author: Ojewole E, Mackraj I, Akhundov K, et al.

buccal mucosal route offers several advantages but the delivery of certain drugs can be limited by low membrane permeability, Aloe vera gel (AVgel) as a novel buccal permeation enhancer, Permeation studies were performed using Franz diffusion cells, and the drug was quantified by UV spectroscopy, buccal permeability properties of didanosine (ddI), permeability of ddI was concentration-dependent, and it did not have any adverse effects on the buccal mucosae, linear relationship (R2?=?0.9557) between the concentrations and flux indicated passive diffusion as the mechanism of drug transport, Aloe Vera gel at concentrations of 0.25 to 2?%w/v enhanced ddI permeability with enhancement ratios from 5.09 (0.25?%w/v) to 11.78 (2?%w/v) but decreased permeability at 4 and 6?%w/v, Aloe Vera gel-treated mucosae showed irregular nuclear outlines, increased intercellular spacing, and plasmalemma crenulations, cells from 1, 2, and 6?%w/v Aloe Vera gel-treated mucosae showed irregular nuclear outlines, increased intercellular spacing, and plasmalemma crenulations

Authors V Kusum Devi 1, Nimisha Jain, Kusum S Valli

Biocompatibility. A measure of how a biomaterial interacts in the body with the surrounding cells, tissues and other factors. A biomaterial is considered to have good biocompatibility if it does not generate a vigorous immune response, resists build-up of proteins and other substances on its surface that would hinder its function, and is resistant to infection. Drug Delivery Systems. Engineered technologies for the targeted delivery and/or controlled release of therapeutic agents. Routes of Delivery. Medications can be taken in a variety of ways—by swallowing, by inhalation, by absorption through the skin, or by injection. Each method has advantages and disadvantages, and not all methods can be used for every medication. Improving current delivery methods or designing new ones can enhance the use of existing medications. novel drug delivery technology is applied in herbal medicine, it may help in increasing the efficacy and reducing the side effects of various herbal compounds and herbs. This is the basic idea behind incorporating novel method of drug delivery in herbal medicines. modern phytopharmaceutical research can solve the scientific needs (such as determination of pharmacokinetics, mechanism of action, site of action, accurate dose required etc.) of herbal medicines to be incorporated in novel drug delivery system, such as nanoparticles, microemulsions, matrix systems, solid dispersions, liposomes, solid lipid nanoparticles and so on. medicinal product on the market have to be accompanied by a dossier containing particulars and documents relating in particular to the results of physico-chemical, biological or microbiological tests as well as pharmacological and toxicological tests and clinical trials carried out on the product and thus proving its quality, safety and efficacy and an acceptable level of safety. Herbal medicinal product: any medicinal product, exclusively containing as active ingredients one or more herbal substances or one or more herbal preparations, or one or more such herbal substances in combination with one or more such herbal preparations; Herbal substances: All mainly whole, fragmented or cut plants, plant parts, algae, fungi, lichen in an unprocessed, usually dried, form, but sometimes fresh. Certain exudates that have not been subjected to a specific treatment are also considered to be herbal substances. Herbal substances are precisely defined by the plant part used and the botanical name according to the binomial system ; Herbal preparations: preparations obtained by subjecting herbal substances to treatments such as extraction, distillation, expression, fractionation, purification, concentration or fermentation. These include comminuted or powdered herbal substances, tinctures, extracts, essential oils, expressed juices and processed exudates. oral, external and/or inhalation preparation. herbal substance, the indication, the specified strength and the posology, the route of administration and any other information necessary for the safe use of the herbal substance as a traditional medicinal product. innovative forms to delivery drugs with herbal excipients as aloe vera, formulation design with final drug product design. We offer end-to-end support for various topical delivery routes, including dermal, nasal/lung, ophthalmic, otic, vaginal/rectal, and ungual. Dermal Delivery. topical and transdermal products, dermatological formulations, develop skin penetration enhancer, optimize formulation design and target engagement against established and customer specific biochemical pathways with range of semi-solid dosage forms including creams, gels, sprays, foams, ointments, lotions, mousses and lacquers, transdermal patches, drug in adhesive to multi-layer. Lung & Nasal Delivery, develop and characterize aloe as vehicle through devices for delivery to the nasal cavity and lung for MDI, DPI and nebulizer formulations. Drug delivery via these routes is attracting growing attention with the dietary supplements, nutrition health and herbal medicine market industry in the space of inhalation formulation development, according with EU regulation for drug delivery products, formulations, and devices in models, optimizing the chances of market success. Development of lung and nasal delivery development. Ophthalmic Delivery. The eye is a complex organ with unique anatomy and physiology, and it can be difficult to overcome its natural protective barriers and aloe as bioenhancer can be effective vehicle for drugs, develop drops, lotions and injectables covering conjunctival, corneal, intravitreal and transscleral routes of delivery, develop specific models for measuring trans-corneal penetration, and optimize formulations and understand the fate of products applied without having to run in vivo trials. Oro-mucosal, Rectal and Vaginal Delivery. Skin enhancement develops a wide range of formulations optimized for mucosal membrane treatment including creams, gels, ointments, suppositories, foams, sprays, lotions, lozenges and films, commercial topical, intravitreal (intra-ocular) and trans-scleral (peri-ocular) herbal products for both immediate and controlled release, Otic Delivery. Developed specific drops, lotions and other topicals for treating outer and middle ear conditions with aloe vera, drops and foams, both of which are effective formulations for treating the ear canal. Ungual and Trans-ungual Delivery. Development drugs for ungual and transungual drug delivery, these products cover a wide range of formulations for treating nails including creams, gels, sprays, lotions, and lacquers.

Author Wo?niak A, Paduch R.

Ocular diseases are currently an important problem in modern societies. Patients suffer from various ophthalmologic ailments namely, conjunctivitis, dry eye, dacryocystitis or degenerative diseases. Therefore, there is a need to introduce new treatment methods, including medicinal plants usage. Aloe vera [Aloe barbadensis Miller (Liliaceae)] possesses wound-healing properties and shows immunomodulatory, anti-inflammatory or antioxidant activities, Corneal epithelium is the most external layer of eye surface and therefore it is especially exposed to various harmful factors, among typical environmental agents influencing corneal lineage uniformity, there are also plant components which could be potentially used in eye drops. To analyze morphology, functionality and viability of corneal layer to chemical stress, we used to establish 10.014 pRSV-T cell line to test Aloe vera extract activity. This evaluation was performed to assess the potential usefulness of Aloe components to be applied in eye drops in the future.

Author Lee A, Chui PT, Aun CST,Gin T, Lau ASC.

patient with massive intraoperative bleeding after oral consumption of Aloe vera tablets, Aloe vera is a common herb used for antiinflammatory and antiarthritic activity, as well as antibacterial, hypoglycemic, and lipid-lowering effects. Compounds contained within Aloe vera can cause a reduction in prostaglandin synthesis, which may inhibit secondary aggregation of platelets, sevoflurane inhibits thromboxane A(2) formation by suppression of cyclooxygenase activity, impairs platelet aggregation, and prolongs bleeding, although the vascularity and size of the hemangioma were the most important factors for the massive intraoperative blood loss, concomitant use of sevoflurane and Aloe vera played a contributory role, an objective causality assessment revealed that this adverse event was possible because of the sevoflurane and Aloe vera interaction, there is a potential herb-drug interaction between Aloe vera and sevoflurane based on the antiplatelet effects of these 2 agents. Herbal medications with antiplatelet potential should be discontinued before anesthesia and surgery.

Author ImS?A,OhS-T,SongS,KimM-R,KimD-S,WooS?S,JoTH,ParkYI, LeeC-K.

Polysaccharides isolated from the gel of Aloe, Immunomodulatory activities, polysaccharides between 400 and 5 KDa exhibit the most potent macrophage-activating activity as determined by increased cytokine production, nitric oxide release, expression of surface molecules, and phagocytic activity

Author: Kulkarni, G.T.; Gowthamarajan, K.; Dhobe, R.R.; Yohanan, F.; Suresh, B.

polysaccharide hydrogel was isolated from the seeds of Tamarindus indica (tamarind) and was used as release modifier for the preparation of diclofenac sodium spheroids, using extrusion-spheronization technique, the process was studied for the effect of variables to arrive at spheroids with satisfactory particle shape, size and size-distribution. The prepared spheroids were characterized for surface morphology, qualitative surface porosity, friability, bulk density, and flow properties, the in vitro release studies exhibited a zero-order release kinetics that was confirmed by Higuchi’s and Peppas’ models. A credible correlation was obtained among swelling index, viscosity, surface roughness of the polysaccharide, and in vitro dissolution profile of the spheroids. In the comparative bioavailability study, we found that the developed spheroids were able to sustain the drug release over 8 hr and could improve the extent of absorption and bioavailability of the drug.

Author: Vinson J A, Al Kharrat H, Andreoli L.

effect of consumption of Aloe vera liquid preparations on the absorption of water- or fat-soluble vitamins, Aloe on the human absorption of vitamins C and E, vitamin supplements, plasma bioavailability of vitamins C and E, supplementation of vitamin C with Aloe Gel area was 304%,For vitamin E, the results for the relative areas increase with aloe Gel 369% of absorption in plasma test, Aloes improve the absorption of both vitamins C and E. The absorption is slower and the vitamins last longer in the plasma with the Aloes. Aloe is the only known supplement to increase the absorption of both of these vitamins and should be considered as a complement to them, recent report showed that Helicobacter pylori infection signi?cantly impairs the bioavailability of vitamin C, amount recommended for vitamin Consumption by the US Government has been increased recently to 75 mg per day for women and 90 mg for men, smokers should add an additional 35 mg per day because their metabolic turnover of vitamin C is more rapid, as is their rate of oxidative stress, study of its pharmacokinetics in humans, it was suggested that the amount be increased to 200 mg/day, representing maximum bioavailability, supplement of C or ingestion of an agent that can increase the absorption of C may be needed, Vitamin E (tocopherol), a lipid-soluble vitamin, Vitamin E can reduce cognitive decline and improve the immune system, Epidemiological studies indicate vitamin E may also reduce the risk of cardiovascular disease, although results from supplementation studies are mixed, Innovaloe from AMB Wellness is processed using the hand-?lleted technique, Hand-?lleted processing removes the inner gel while avoiding the yellow latex found next to the rind, Aloe gel extract was especially effective in slowing down and increasing the absorption of ascorbate, Aloe extracts improved the absorption of vitamin E and prolonged its plasma concentration, especially after 8 h. Aloe is unique in its ability to improve the absorption of both of these vitamins and should be considered as an adjunct for people who take vitamin supplements

Author: Boudreau M D, Beland F A.

Aloe barbadensis (Miller), a topical and oral therapeutic, Herbal remedies are used either as topical agents or as dietary supplements for both general health promotion and the specific treatment of ailment symptoms, consumption at various concentrations in liquid, powder, and tablet form, ingestion of Aloe vera, smaller oligosaccharides in this carbohydrate fraction have been proposed to be absorbed in complete form via pinocytosis and enter the blood stream unchanged

Author Liu C, Leung MY, Koon JC, et al..

mannose-rich polysaccharide biological response modifier, stimulatory activity, potent stimulator of murine macrophage, tumoricidal properties of activated macrophage, Polysaccharides, Biological response modifier, Aloe vera, Macrophage, Aloe, chemistry, Animals, Antineoplastic Agents, pharmacology, Cell Line, Tumor, Histocompatibility Antigens Class II, biosynthesis, Immunologic Factors, isolation & purification, Macrophage Activation, drug effects, Macrophages, Peritoneal , immunology, metabolism, Mice, Mice, Inbred BALB C, Nitric Oxide, Phagocytosis, Receptors, IgG, Tumor Necrosis Factor-alpha, Biological response modifier ,Aloe vera Macrophage

Author Abolfazl Aslani, Alireza Ghannadi, Razieh Raddanipour

design and evaluate the formulation of Aloe vera chewing gum with an appropriate taste and quality with the indications for healing oral wounds, such as lichen planus, mouth sores caused by cancer chemotherapy and mouth abscesses as well as reducing mouth dryness caused by chemotherapy, Aloe vera powder, the carbohydrate content was determined according to mannose and phenolic compounds in terms of gallic acid, chewing gum was cut into pieces of suitable sizes. Weight uniformity, content uniformity, the organoleptic properties evaluation, releasing the active ingredient in the phosphate buffer (pH, 6.8) and taste evaluation were examined by Latin square method, healing properties of Aloe vera improve the skin which is exposed to ultraviolet (UV) and gamma rays. It has antiinflammatory, antiseptic, antiviral, antibacterial, antitumor, moisturizing, antiaging, hypoglycemic, antidiabetic, cytotoxic, and antioxidants effects. It is also used against cardiovascular diseases, pharmaceutical chewing gums are produced in a solid form and a single dose. Their base mainly consists of gum base. This form of medication contains one or more active ingredients that are released by chewing. Pharmaceutical applications of pharmaceutical chewing gums include topical treatment of oral diseases and systemic delivery after absorption through the buccal mucosa or the gastrointestinal route, benefits of chewing gum include consumption without water ,high acceptance by children, low side effects, suitable stability, high bioavailability, rapid onset effect and relieving the mouth dryness by stimulating saliva, formulation of pharmaceutical chewing gums contain pharmaceutical active ingredients, gum bases, fillers, elastomers, plasticizers, softeners, emulsifiers, sweeteners and flavors, factors affecting drug release in this type of dosage form include physicochemical properties of the active ingredient, chewing gum properties and related factors with strength and number of masticatory movements, some of the formulated drugs in the form of chewing gum include fluoride, chlorhexidine, nicotine, aspirin, caffeine, and dimenhydrinate, oral Aloe vera can be used as a wound healer for oral wounds, To heal mouth sores, such as lichen planus, ulcers and abscesses caused by cancer chemotherapy, oral products such as mouthwash are used. Recently, one study examined the effects of 70% Aloe vera extract in the form of mouthwash for the treatment of mucositis caused by radiotherapy and another study examined the effects of 80% Aloe vera extract in the form of mouthwash to treat lichen planus

Author: Habeeb F, Stables G, Bradbury F, et al.

anti-microbial effects of the inner gel from Aloe barbadensis Miller (syn. Aloe vera (L.) Burma. f. or Aloe vera), Infection is usually restricted to the top layer of colonic mucosa, where it causes ulceration and severe tissue damage, e pharmacology of natural products, blood leukocytes to show that both pro-inflammatory cytokines induced by whole bacterial stimulation can be suppressed with at least 45mg/ml inner gel (final concentration in assay 4.5 mg/well), while a tenfold dilution was only effective against TNF-a.

Author: Di Colo G, Zambito Y, Zaino C.

drug delivery ,absorption enhancer, permeation enhancer , polymeric biomaterials, polymer synthesis, chitosan, paracellular, transport transcellular, transport tight junction , transmucosal drug administration across nasal, buccal, and ocular mucosae is noninvasive, eliminates hepatic first?pass metabolism and harsh environmental conditions, allows rapid onset, and further, mucosal surfaces are readily accessible, hydrophilic drugs, such as peptides and proteins, are poorly permeable across the epithelium, which results in insufficient bioavailability, reversible modifications of epithelial barrier structure by permeation enhancers are required, Low molecular weight enhancers generally have physicochemical characteristics favoring their own absorption, polymeric transmucosal penetration?enhancers, intestinal permeation enhancers, synthesis and characterization of polymers, their effectiveness in enhancing the absorption of different drugs across different epithelium types, their mechanism of action and structure?efficacy relationship

Author: Kathryn A Whitehead, Samir Mitragotri

needles are the primary mode of administering macromolecular drugs such as proteins and peptides, their limitations have motivated researchers to explore alternative routes. One of the most popular alternatives to parenteral drug administration is oral delivery, which requires transport across the intestinal epithelial membrane. Because the epithelium protects against the entry of xenogenic sub-stances into the body, it also acts as a barrier to the delivery of macromolecules, this issue of limited transport can be potentially addressed through the use of chemicals to promote drug absorption across the epithelium, Chemical permeation enhancers aid drug uptake through two distinct mechanisms, both of which involve the mediation of a physical cellular barrier, the passive transcellular route involves the alteration of the structure of the cell membrane, whereas an enhancement of the paracellular route entails an opening of the tight junctions between epithelial cells, many studies have focused their efforts on ascertaining the mechanism of action of a variety of enhancers, Specifically, enhancer mechanism is typically considered to be solely transcellular or paracellular

Author: Sudhakar Y, Bandyopadhyay AK.

white mustard mucilage from whole seeds of Sinapis alba was evaluated for its physical properties and compared with the other mucoadhesive polymers such as hydroxy propyl methylcellulose 5Cps and Carbopol 934P. Further, methanol precipitable solids from whole leaves of Aloe Vera L were used as permeation enhancer, to achieve improved bioavailability of diltiazem, novel buccal adhesive tablets (NBATs) in cup and core fashion designed to achieve unidirectional release towards mucosa were prepared in a three-stage process using specially fabricated punches. The adhesive cups were studied for its shear, tensile, and peel strengths by specially designed apparatus using excised ruminant and porcine buccal mucosa as model substrates. Ex vivo permeation studies in a Franz diffusion cell were conducted through porcine buccal mucosa. Fourier transform infrared spectroscopy studies and differential scanning calorimetry thermographs showed no remarkable interactions. Histopathological studies showed no remarkable damage of buccal mucosa by the NBATs. In vivo studies were conducted on anaesthetized male New Zealand albino rabbits, estimated by reversed-phase high-performance liquid chromatography, and the pharmacokinetics were compared with the oral and intravenous bolus injection. NBATs exhibited a Cmax 74.6 ng/mL, Tmax 3.5 h, t1/2 4.36 h. The NBATs prevented salivary scavenging effect and exhibited 82.1% bioavailability.

Authors Robert H. Davis

Aloe vera as a biological vehicle for the delivery of drugs, Aloe vera is used as a biological vehicle to deliver the estrogen, beta -estradiol and the androgen, testosterone propionate, provide treating symptoms and diseases mediated by hormonal deficiencies or amenable to treatment by hormones using Aloe vera as a biological vehicle, for treating hormonal deficiencies and conditions amenable to treatment with hormones using Aloe vera as a biological vehicle for delivery of the hormone, Aloe compounds having diverse biological activities, including anti-tumor activity, anti-gastric ulcer, anti-diabetic, anti-tyrosinase activity, and antioxidant activity, Aloe can be used as a vehicle for delivering the corticosteroid, hydrocortisone, administered both topically and subcutaneously, to the site of inflammation, This study revealed that Aloe vera contributed in an additive way to the activity of the steroid, suggesting that Aloe vera may be useful as a biological vehicle for hydrocortisone. The significance of this finding is that if used in combination with Aloe vera, the dosage of the steroid can be reduced, while maintaining its biological activity, thereby reducing or eliminating any toxic side effects associated with higher dosages. These studies also revealed that Aloe vera assists in the penetration of hydrocortisone through the stratum corneum. Since Aloe vera contains many hydrophilic compounds, such as enzymes, amino acids and carbohydrates, as well as, hydrophobic compounds, such as vitamins and sterols, Davis et al. postulate that pharmacologic agents of both solubilities can be placed in Aloe vera and carried through the epidermal barrier, A vehicle is a substance, usually without biological activity, which is used as a medium for the administration of pharmacologic agents. Ideally a vehicle should be nonirritating and compatible with common medications. Criteria for vehicle selection include solubility of the active agent in the vehicle and the ability of the vehicle to penetrate physical barriers such as the stratum corneum and the lipid portion of the cell membrane. Consideration must also be given to any interactions between the vehicle and the active agent, the efficiency with which the vehicle releases the incorporated active ingredient, the molecular size and the composition of the vehicle. Traditional vehicles for subcutaneous administration include oils which tend to be irritating. Aloe vera has been shown to be nonirritating and nontoxic when injected subcutaneously in mice, even at massive doses, a vehicle will have a synergistic effect, such that the final sum total of the activity in each system is greater than the sum of the components. As stated above, this is highly desirable in that less of the pharmacologic agent can be used to achieve the same effect, thereby reducing or eliminating any side effects associated with higher dosages.

Author: Tae Hyung JO, Seon Gil Do, Eun Ju Shin, Hye In Jang, Jin Wan Kim, Ghe Whan Ahn, Seung Won Yang, Jin Hee Im, Jeong Bum Nam, Soo Gyeom Kim , Ken Jones

aloe vera sprout concentrate or extract having cell growth promotion, antioxidant, and anti-allergy effects, and to a skin cell growth promoting, antioxidant, and anti-allergy pharmaceutical composition and functional health food or cosmetics containing the aloe vera sprout concentrate or extract as an active ingredient, present invention is to provide an Aloe vera shoot concentrate or extract which has the effects of promoting cell regeneration and cure healing, and has excellent antioxidant and anti-allergic effects, and a pharmaceutical composition for promoting skin cell proliferation, antioxidizing, or preventing or treating allergic disease or symptom, and a health functional food, Antioxidant action is a process to remove active oxygen species. Active oxygen species in the body are generated from general cell metabolism, and hydrogen peroxide (H2O2) is a representative substance. Such active oxygen species can impair cells and are regarded as a main cause of aging. In cells, catalase, superoxide dismutase (SOD) and the like convert hydrogen peroxide into oxygen and water to decrease impairment, Allergy is a hypersensitive immune response to external foreign substances. Representative example is allergic rhinitis, allergic asthma, allergic dermatitis, allergic conjunctivitis or allergic gastrointestinal disease. In case of adult aloe, it has been reported that alprogen—which is one of the glycoproteins—is effective in the treatment of allergy by suppressing release of the inflammatory mediators, histamine and leukotriene, in a concentration-dependent manner

Author: Qiu Z, Jones K, Wylie M, Jia Q, Orndorff S.

activated macrophage cells and stimulated fibroblast growth, average molecular weight of 80,000 Dalton (Da), mannose, galactose, and glucose, fibroblasts, growth, neoplasms, hypersensitivity, ep,dermis, macrophages, polysaccharides Ultraviolet radiation, irradiation, mannose, immunosuppression

Author: Ward, P.D.; Tippin, T.K.; Thakker, D.R.

intestinal epithelium is a major barrier to the absorption of hydrophilic drugs. The presence of intercellular junctional complexes, particularly the tight junctions (zona occludens), renders the epithelium impervious to hydrophilic drugs, which cannot diffuse across the cells through the lipid bilayer of the cell membranes, design of agents that can effectively and safely increase paracellular permeability via modulation of tight junctions, the tight junction barrier function is physiologically important, in that it maintains electrolyte gradients and membrane polarity and keeps macromolecules out of the body,

Author: Yagi A, Hamano S, Tanaka T, Kaneo Y, Fujioka T, Mihashi K. Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Fukuyama, Japan.

Aloemannan – Aloe vera – Asphodelaceae – fluoresceinyl isothiocyanate aloemannan – metabolism – degraded fluoresceinyl thiocyanate aloemannan – fast atom bombartment mass spectrometry – matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

Author Barry, B.W.

Skin enhancement, Iontophoresis, Ultrasound, Liposomes, Optimization of drug delivery through human skin is important in modern therapy. This review considers drug–vehicle interactions (drug or prodrug selection, chemical potential control, ion pairs, coacervates and eutectic systems) and the role of vesicles and particles (liposomes, transfersomes, ethosomes, niosomes) , modify the stratum corneum by hydration and chemical enhancers, or bypass or remove this tissue via microneedles, ablation and follicular delivery. Electrically assisted methods (ultrasound, iontophoresis, electroporation, magnetophoresis, photomechanical waves) show considerable promise. Of particular interest is the synergy between chemical enhancers, ultrasound, iontophoresis and electroporation.

Authors Delly Ramadon, Maeliosa T. C. McCrudden, Aaron J. Courtenay & Ryan F. Donnelly

Transdermal drug delivery systems , research topic in pharmaceutical technology area, developed pharmaceutical products in global market, delivery routes, such as oral and parenteral, applications of transdermal technologies, transdermal drug delivery systems and enhancement strategies, development of first-generation transdermal products, drug/vehicle interactions, vesicles and particles, stratum corneum modification, energy-driven methods and stratum corneum bypassing techniques, suitable design and implementation of active stratum corneum bypassing methods, notably microneedle technology, transdermal delivery systems have been shown to deliver both low and high molecular weight drugs, microneedle technology platforms, intradermal delivery of drugs/biotherapeutics and therapeutic drug monitoring, strategy for improving transdermal delivery systems, drug delivery systems, Innovation in drug delivery systems is a key strategy employed to improve the bioavailability of active pharmaceutical ingredients (APIs), oral delivery systems offer benefits , such as dosage form variety, painless ease of administration, convenience, self-administration, high safety, and patient compliance , oral delivery systems have some limitations such as poor drug stability in the gastrointestinal tract and subjection to first pass metabolism. For instance, there is a possibility of drug degradation caused by enzymatic reaction or exposure to the acidic environment in the stomach, solubility issues of drugs in the intestinal fluid and their permeability through the intestinal membrane may act as rate limiting steps in drug absorption, causing low bioavailability these drawbacks are routinely observed in the delivery of peptide or protein-based drugs, as a result, intravenous (IV) injection is designated as one of the most promising delivery system for proteinaceous drugs, as it can achieve up to 100% bioavailability, accurate dosing and hepatic metabolism avoidance, injection can achieve up to 100% bioavailability, accurate dosing and hepatic metabolism avoidance, disadvantages are an invasive delivery method, causing pain, low patient compliance, and sharps waste disposal considerations add significant costs, transdermal drug delivery systems use the skin as the drug administration site, the administered drug is absorbed into the systemic circulation via blood vessels in the skin and then circulates around the body, transdermal drug delivery systems offer some advantages for patients, such as being less invasive (some methods are entirely noninvasive), first-pass metabolism avoidance, ease of application and administration, reduce frequency of administration, used for the delivery of different varieties of drugs, both hydrophilic and hydrophobic compounds, Drug absorption via the skin, application of drug-containing dosage forms onto the skin, drug will be released into the skin, Avoidance of significant pre-systemic metabolism (degradation in gastrointestinal tract (GIT) or by the liver) leading to bioavailability improvement, continuity of drug administration in transdermal patches permits the use of a drug with short biological half-life, possibility of sustained and controlled drug delivery over a prolonged period of time even drugs with narrow therapeutic window, Increased patient acceptance and compliance due to the reduction of dosing frequency , more uniform pharmacokinetic profiles of drugs with minimization of peaks-troughs in plasma-drug concentration, thus reducing the risk of toxic side effects, Ease of dose termination in case of any systemic or local adverse effect, providing an alternative to oral dosing in the circumstances of unconscious or nauseated patients, facilitating noninvasive mode of drug administration by avoiding the risk and inconveniences such as needle phobia associated with parenteral therapy, in spite of many potential advantages, transdermal patches has following limitations, essentiality of molecular weight <500 Da to ensure ease of diffusion across the SC, since solute diffusivity is inversely related to its size, Sufficient aqueous and lipid solubility, a Log P (octanol/water) in between 1 and 3 is required for the permeant to successfully traverse the SC and its underlying aqueous layers for systemic delivery to occur, drugs that require high blood levels cannot be administered as transdermal patches is mostly limited only to potent molecules (oral dose is <10 mg/day) , certain drugs, excipient, or components of transdermal patches may cause skin irritation and sensitization leading to erythema and edema, intra- or inter-personal variability in skin changes its barrier function, drug administration in transdermal patches permits the use of a drug with short biological half-life (2–4 h),

Author: Narayana Charyulu Rompicherla , Punam Joshi 1, Amitha Shetty, Kalvatala Sudhakar ,Hawraz Ibrahim M. Amin , Yachana Mishra, Vijay Mishra , Aqel Albutti * and Naif Alhumeed

Topical treatments are a potential therapeutic option for the therapy of osteoarthritis, with significant data supporting the effectiveness and safety of topical formulation. Topical gel formulations may offer an alternative to oral formulations to relieve osteoarthritis (OA) pain while decreasing systemic exposure. Topical capsaicin transemulgel may represent an effective and safe alternative. The transemulgel was prepared from aqueous Aloe vera gel and Carbopol 934 with capsaicin in clove oil emulsion, improved permeability properties. The formulation caused no skin irritation when applied topically, emulsion, capsaicin, arthritis, topical, anti-inflammatory agent, drug delivery, Osteoarthritis is the most common degenerative joint disease, Pathological changes in osteoarthritis joints include destruction of articular cartilage, progressive loss, subchondral bone thickening, osteophytes formation, ligament degeneration, menisci of the knee, and hypertrophy of the joint capsule, treatment includes oral and topical pharmacological agents, patient education, alternative surgery, medicine, physical therapy, and modalities, topical drug delivery has advantages over conventional routes; in particular, it avoids first-pass metabolism, and is a non-invasive mode of drug delivery with a sustained and controlled release profile, Aloe vera (Aloe barbadensis miller), a perennial plant belonging to the family Liliaceae, is used due to its anti-inflammatory, anticancer, antimicrobial, immunomodulatory, and burn healing effects. It has been used in different commercial products, due to its cooling effect, the burning sensation of capsaicin can be reduced by rubbing the skin with Aloe vera gel as a base,therefore, the present research work aimed to develop and evaluate capsaicin transemulgel using Aloe vera gel as a base for the treatment of osteoarthritis

Author Tafara Jambwa, Alvaro Viljoen, Josias Hamman

pharmaceutical industry endeavours to develop novel drug delivery systems which require excipients that full specific functions. Excipients from renewable sources are attractive due to their sustainable mass production. The purpose of this study is to investigate the potential use of gel and whole leaf materials from Aloe vera as excipient in the formulation of controlled release matrix-type mini-tablets, Matrix-type mini-tablets manufactured from the aloe materials alone, and in combination with other polymers were evaluated in terms of their physical characteristics, mucoadhesive properties, swelling behavior and drug release kinetics. Some of the formulations exhibited high potential to control drug release from matrix-type tablets and some approached zero-order kinetics, A disadvantage of the conventional immediate-release tablet as dosage form is that drug plasma levels fluctuate over successive doses, ,modification in drug-release rate, such as controlled release, may be beneficial in eliminating the cyclic fluctuations in drug plasma levels , Polymers used in dosage form design can be classified as synthetic polymers, semi-synthetic polymers and polymers of natural origin, Natural polysaccharides are often obtained from plants in the form of mucilages and gums. In many cases, the properties of a natural polymer do not t the needs of a specific application and blending with a synthetic polymer can sometimes be used to achieve the desired properties , Multiple-unit dosage forms over several advantages over conventional single-unit dosage forms. They contain a number of sub-units in which the dose is the sum of the quantity of the drug in each sub-unit. Examples include granules, pellets or mini-tablets that can be formulated into a single, hard gelatin capsule, Formulations containing the different aloe powders individually, and in combination with either Carbopol® or hydroxypropyl methylcellulose in different ratios, aloe leaf materials are suitable as excipients in the design and development of matrix-type tablets for modified drug release, the formulation containing Aloe Vera Gel and Carbopol in a 50:50 ratio, indicating aloe vera gel powder has potential as excipients in combination with other polymers to form matrix systems that can control drug release

Author: Jun Wu ,Ying Zhang,Zhongming Lv,Ping Yu,Weiqing Shi

Aloe vera has been widely used in health and nutritional supplements, Aloe vera soft capsule (ASC), safety evaluation of Aloe vera products before marketing, aloe vera not produce any marked subacute toxic effects, ASC showed no mutagenic activity in the Ames test and no evidence of potential to induce bone marrow micronucleus or testicular chromosome aberrations in ICR mice exposed to 10000 mg/kg bodyweight. Collectively, ASC could be considered safe before it was marketed as a laxative and moistening health food.

Author: Gerardo Daniel Sierra-Garcíaa , Rocío Castro-Ríosc , Azucena González-Hortaa , Jorge Lara-Ariasb and Abelardo Chávez-Montes

Acemannan medicinal, properties like osteogenic, anti-inflammatory, and antibacterial, accelerate healing of lesions, antiviral , antitumor activities in vivo through activation of immune responses, immune-stimulating [9], anti-neoplasic [10] and wound-healing actions, Biochemistry of acemannan, Acemannan, a ?-(1, 4)-linked polydispersed, highly acetylated mannan, is found in the inner leaf gel of the aloe plant, where it is produced by a specialized cells called leucoplasts, As a polysaccharide, acemannan is composed of mannose, glucose and galactose monomers. The approximate monosaccharide composition of acemannan is 31 ?-(1, 4)-linked mannoses, 1 ?-(1, 4)-linked glucose, and 1 ?-(1, 6)-linked galactose, Acemannan is one of the polysaccharides that dramatically increase white blood cell, macrophage and T cell numbers, activation of macrophages, acemannan, in combination with interferon gamma, has an effect on the release of nitric oxide, interleukin-6 and tumor necrosis factor-? by macrophages ,Release of these cytokines stimulates an increase of up to 300% in the replication of fibroblasts in tissue culture and enhances macrophage phagocytosis, hematoaugmenting properties by increasing peripheral and splenic blood cellularity in hematopoietic progenitors in mielosuppressed mice , and has been shown to upregulate function and generation of cytotoxic T-lymphocytes, immnunomodulatory activity also on dendritc cells by inducing maturation of these cells, recognition of terminal mannose by macrophages as a foreign substance due to it being common on the polysaccharides and oligosaccharides produced by microorganisms, acemannan allows the production of cytokines, interleukin-6, interferon gamma and tumor necrosis factor, the release of nitric oxide, which in turn is related to receptors for mannose monosaccharide, and candicidal activity by phagocytes. It is also known that increasing the antigen expression on the cell surface is a consequence of the release of gamma interferon, allowing increased expression of the molecules of the major histocompatibility complex; in this case it would carry the Class I viruses on the surface of the cell and would ensure their recognition by cytotoxic T cells to be eliminated. Another mechanism implicated by acemannan is inhibition of opsonization, the production of specific antibodies and the induction of delayed hypersensitivity; all these are responsible for the immunomodulatory effect of Aloe

Author Sasan Khadem nematollahi1 , Abbas Pardakhty2, Kobra Habibi3 , Mitra Mehrabani3

effectively deliver these biologicals, Niosomes are vesicles composed of non-ionic surfactants, which are biodegradable, relatively nontoxic, more stable and inexpensive, an alternative to liposomes, application in medicine, preparation of niosome, types of niosomes, characterisation and their applications, Bilayer, drug entrapment, lamellar, niosomes, surfactants, targeted drug delivery, designed for attempting to concentrate the drug in the tissues of interest while reducing the relative concentration of the medication in the remaining tissues, Different carriers have been used for targeting of drug, such as immunoglobulin, serum proteins, synthetic polymers, liposome, microspheres, erythrocytes and niosomes, self-assembly of non-ionic surfactants into vesicles, hydration are microscopic lamellar structures formed upon combining non-ionic surfactant of the alkyl or dialkyl polyglycerol ether class with cholesterol, encapsulated glucomannan in vesicles, release of the polysaccharides, Encapsulation efficiencies, Niosomes could be used for topical delivery of Aloe gel due to slow diffusion-based release rate of Aloe gel and the high stability of the prepared vesicles. Lipid vesicles have penetration enhancing properties, hopefully resulted in better efficacy of the gel in topical administration, Glucomannan

Author Sneha Bahuguna, Deepika Joshi*, Bhavana Singh and Nidhi Semwal

Delivery of herbal drugs as novel formulations faces hurdles due to difficulties in identification, processing, standardizing, extracting of herbal drugs with an intention to accomplish sustained and controlled release. Now with the innovation in the technologies, nano formulations paves pathway for the development of novel herbal drug delivery systems with enhancing bioavailability, therapeutic effect and reduced toxicity. Many novel carriers such as nanoparticles, phytosomes, liposomes, microemulsion, etc. have been reported for successful modified delivery of various herbal drugs. Nano formulation shows various benefits conventional delivery approach such as enhanced absorption, bioavailability and reduction in side effect, novel approaches used for improving safety and efficacy of such herbs, type of active ingredients used for developed nano formulations of herbal drugs for dermal care to achieve better therapeutic response, herbal medicament can solve the scientific needs (such as determination of lethal dose, therapeutic dose, pharmacokinetics parameters, mechanism of action, site of action, suitable route of administration etc.) for developing novel drug delivery system, such as solid lipid nanoparticles, solid lipid microspheres, micro-emulsions, dermal and transdermal patches, solid dispersions, liposomes, phytosomes, ethosomes and nanoparticles.

Author Imran KT, Gore S, Giradkar P.

treatment of illness has been accomplished by administrating drugs to human body via various routes namely oral, sublingual, rectal, parental, topical, inhalation etc. Topical delivery can be defined as the application of a drug containing formulation to the skin to directly treat cutaneous disorders like acne or the cutaneous manifestations of a general disease like psoriasis with the intent of containing the pharmacological or other effect of the drug to the surface of the skin or within the skin. Semi-solid formulation in all their diversity dominates the system for topical delivery, but foams, spray, medicated powders, solution, and even medicated adhesive systems are in use, The delivery of a drug to a specific site, topical formulations are probably among the most challenging products to develop. An effective topical formulation needs to provide a stable chemical environment in a suitable dispensing container to accommodate multiple compounds that may have different, if not incompatible, physicochemical characteristics, once applied, a topical formulation must interact with the skin environment, which can influence the rate of the release of the compounds in order to achieve adequate skin absorption, The excipients themselves will exert additional physical effects on the skin, such as drying, occluding, or moisturizing, technology have brought a better understanding of the physics, chemistry, pharmacodynamic, and pharmacokinetics for drugs used to treat acne. These insights have resulted in new delivery systems that are capable of enhancing the efficacy, tolerability, and cosmetic acceptability of topical formulations Topical drug delivery offers the advantages of ease of delivery, a cooperative patient, increased compliance as well as the avoidance of first-pass metabolism, New drug delivery technology and penetration enhancers, There are important issues to consider as you contemplate development of a topical dermatological product. You may already have experience with oral or parenteral products, but there are challenges and issues which are unique to development of topical formulations, A topical formulation must be aesthetically pleasing, in addition to being both physically and chemically stable, and this may require numerous excipients. The formulation must allow for optimal penetration of the drug into the skin, a complex tissue. Skin pH is approximately 5.5; thus the pH of the formulation may change following application to the skin.

Author Anurapa C, Suseem S.R*

oral control delivery system of highly water soluble drug using aloe vera powder as a carrier for matrix tablet. Ascorbic acid is taken as a model drug for its high solubility. Different concentrations such as 30 %, 40 % and 50 % of matrix tablets of Aloe Vera powder are made by wet granulation technique using starch paste as a binder, The formulated granules were further subjected to Quality control test such as Angle of repose (º), Bulk Density, Carr’s Index and Hausner ratio. These matrix tablets are then subjected to in vitro drug release using USP dissolution apparatus. The amount of ascorbic acid released from the matrix is estimated by using UV spectrometer and this result is compared with marketed ascorbic acid tablets. Formulation containing 40 % matrix was found to be good as compared to other two formulations and shows better controlled release of drug, Ascorbic acid tablet, Aloe Vera powder, Water soluble drug, Controlled drug delivery, route of drug delivery is Oral ingestion due to ease of administration and least sterility constraints, pain free administration, tablets may be formulated to offer rapid drug release or controlled drug release, the latter reducing the number of daily doses required, Oral controlled release of drugs with constant release rate has always been a challenge to the pharmaceutical field. There is a high possibility of faster rate of drug release for water soluble drugs if not formulated properly and likely to produce the toxic concentrations, when administered orally, for oral control delivery system of highly water soluble drug using Aloe Vera powder as a carrier for matrix tablet, ascorbic acid is taken as a model drug for its high solubility, Aloe Vera powder was used as a matrix which is naturally occurring and is most frequently used as drug carrier in pharmaceutical studies. Different concentrations, 30 %, 40 %, 50 % of matrix tablets of Aloe Vera powder are made by wet granulation technique using starch paste as a binder. The amount of ascorbic acid released from the matrix is estimated by using UV spectrometer and this result is compared with marketed ascorbic acid tablets, Aloe Vera based matrix tablets were prepared by wet granulation method using starch paste as binder, Aloe Vera Powder has acceptable flow properties and was further used for tablet formulations, out of three formulations prepared 40 % matrix contained formulation was found to be good , shows controlled release of drug whereas marketed drug show high release rate at first hour and then release rate was decreasing slowly

Author: OJHA KHYATI, SHENOY VRANDA, GUPTA SAUMYA, SUSEEM S.R. 2*

develop a controlled release hydrogel and to evaluate the efficiency of its drug delivery, synthetic polymer drug carriers will be safely metabolized, they will not impart any health benefit unlike the natural carriers such as starch and Aloe vera, release characteristics of ascorbic acid based hydrogel formulated using Aloe vera gel powder as a drug carrier and nutrient fortifying excipient, Metabolic equilibrium is maintained in homeostasis but an imbalance in it can lead to oxidative stress. Many medicaments in the form of antioxidants are presently available but they are not effective in the bioavailability because of their rapid systemic drug release patterns, systemic release patterns are not uniform as the drug delivery is not of controlled form, neither are they targeted in their action, recent approach in drug delivery systems is targeted drug delivery system where in many delivery forms are possible such as hydrogels, liposomes, resealed erythrocytes, niosomes, nanoparticles, microspheres and magnetic microspheres. Hydrogel is a recent approach wherein the shortcomings of conventional dosage forms have been circumvented with the introduction of controlled release dosage forms. They are capable of controlling the rate of drug delivery, leading to more sustained drug levels further it increases their systemic availability and thus leads to an increased therapeutic action, hydrogel is a three-dimensionally cross-linked hydrophilic polymer network that may absorb and retains large amount of water up to thousands of times its dry weight. The excellent biocompatibility property of hydrogels makes them most promising for applications such as tissue engineering and drug delivery, natural carrier such as Aloe vera gel powder having inherent tremendous medicinal values. It is noted that Aloe vera gel powder may enhance the intestinal absorption, effective delivery of poorly absorbable drugs, sustained release of pharmaceutical dosage forms, protection against degradation of vitamins and the enhancement of bioavailability of vitamin C. When taken internally along with the drug it may improve the digestive Musculo-skeletal and immune-related conditions apart from acting as an antioxidant, gelatin starch mediated hydrogel is a very novel approach as till date research have not been performed using gelatin and starch combined with Aloe vera gel powder and poly vinyl pyrrolidone. The cross-linker used poly vinyl pyrrolidone helps in cross-linking by providing framework to the hydrogel, Hydrogels of natural polymers, especially polysaccharides, have been used recently because of their unique advantages. Polysaccharides are, in general, non-toxic, biodegradable and abundant, moreover, natural polymers are biocompatible and enhance the drug release efficacy with reduced toxicity and improved patient compliance with in vivo degradation

Author: W Chen, J Hamman, A Vlijoen – African Journal of Traditional,

Oral drug delivery is considered as the preferred route of administration, but the bioavailability of orally administered hydrophilic, macromolecular drugs is usually poor because of the hostile gastric environment and also poor gastrointestinal mucosal permeability. Co-administration of absorption enhancers is one way to improve oral bioavailability of these drugs. Numerous classes of compounds have been reported to enhance the intestinal absorption of poorly absorbable drugs, but most of them have toxic effects and are not highly efficient. Therefore, development of safe and effective absorption enhancers is still a challenge. The effect of Aloe vera (L.) Burm.f. (Aloe barbadensis Miller) gel and whole leaf extract on the permeability of Caco-2 cell monolayers was determined. Both the A. vera gel and whole leaf extract were able to significantly reduce the transepithelial electrical resistance of the Caco-2 cell monolayers at concentrations above 0.5 % w/v and thereby showed the ability to open tight junctions between adjacent cells. This effect was fully reversible as the electrical resistance of the cell monolayers returned to the original value upon removal of the test solutions. The A. vera gel and whole leaf extract solutions significantly enhanced the transport of insulin across the Caco-2 cell monolayers compared to the control. The results suggest that these plant products have a high potential to be used as absorption enhancers in novel dosage forms for drugs with poor bio availabilities when administered orally, The co-administration of absorption enhancing agents with macromolecular drugs (e.g., protein and peptide drugs) has been identi?ed as a means to improve the oral bioavailability of these drugs. Absorption-enhancing agents of natural origins, Aloe vera; gel; whole leaf; absorption enhancement; Caco-2; confocal laser scanning microscopy; F-actin; FITC-dextran; tight junctions; transepithelial electrical resistance

Author Talmadge J, Chavez J, Jacobs L, et al.

Aloe vera L. plant have demonstrated multiple clinical activities, hematopoietic activities of Aloe vera extracts , organ-specific in vitro molecular profile , Preclinical studies have shown that such carbohydrate-containing extracts promote wound repair, augment reticuloendothelial function, modulate immune responses , and function as an anti-neoplastic, stimulate hematopoiesis, Aloe vera gels are composed predominantly of insoluble plant cell wall material, soluble carbohydrates, calcium malate, and a small amount of protein , carbohydrates are composed of long-chain polydispersed h-(1,4)-linked acetylated polymannan with interspersed O-acetyl groups and a mannose monomer/acetyl ratio of approximately 1:1. Pharmacological properties appear to be mainly mediated by the activation of monocytes-macrophages, and extracts of Aloe vera have been reported to enhance the release of cytokines, including interleukin (IL)-1, IL-2, IL-6, interferon (IFN), granulocyte/monocyte-colony stimulating factor (GM-CSF), and tumor necrosis factor (TNF) in vitro, augmentation of reticuloendothelial functions, humoral and cell-mediated immune response, tumor therapy, and hematopoietic proliferation and differentiation, These activities are thought to be secondary to the stimulation of histiocytic lineage cells, resulting in increased secretion of cytokines and enhanced cellular function, Acemannan has been shown to activate macrophages in vitro and vivo

Author Patel , Chopra , Simran Chaurasia

As per Biopharmaceutical Classification System (BCS), one of the main concerns is low solubility and/or permeation of drugs resulting in reduced absorption and poor bioavailability, to overcome these issues, various strategies have been adopted, including the use of permeation enhancers which are also known as bioenhancers, bioenhancers are synthetic or natural compounds that increase the bioavailability of drugs and nutrients such as vitamins, amino acids, minerals, etc., into the systemic circulation and at the site of action for exhibiting improved therapeutic action, by improving bioavailability, bioenhancers can reduce drug dose, decrease the treatment period, and circumvent the problem of drug resistance, plant based bioenhancers can serve as a better alternative owing to their natural origin, plant-based bioenhancers have been used in a wide variety of antibiotics, antiviral, and anti-cancer therapeutics, these can be categorized based on their sources and mechanism of action

Author: DEVARAJ SRIDEVI ET AL

Vitamin/supplement intake is associated with decreased mortality, Aloe vera, a botanical is consumed by 50% of the US population and may affect bioavailability of vitamin, Aloe improved vitamin C absorption. Since oral B12 is deficient in vegetarians and in aging, bioavailability of vitamins, C and B12, in older healthy human volunteers, Aloe vera juice with vitamins B12, 1mg and vitamin C 500 mg, blood was obtained fasting and following 1,2,4,6,8 and 24 hours post-ingestion of aloe/water with 1 week between treatments, Aloe vera Gel significantly increased plasma Oxygen radical absorbance capacity (ORAC), Aloe Gel significantly increased plasma vitamin C , Aloe vera Gel significantly increased serum vitamin B12 levels , Aloe preparations are well-tolerated and enhance bioavailability of vitamins C and B12 and ORAC. This could have major implications with regards to supplementation of vitamins to target chronic diseases, especially in elderly.

Author Prajakta N. Dongare, Anuja S. Motule, Mahesh R. Dubey, Manisha P. More, Prerna A. Patinge , Ravindra L. Bakal and Jagdish V. Manwar

Ethno-botanical information of such plants and their usage by indigenous cultures is useful in the conservation of traditional system of medicine, biodiversity, to promote health care system, therapeutic effects, Novel drug delivery systems for delivery of herbal drugs possesses several advantages over conventional formulations, an optimum amount of the concerned drug is administered to the patient in such a way that it reaches exactly the site of action’ and produce therapeutic effects, some drugs have an optimum concentration range within which maximum benefit is derived, and concentrations above or below this range can be toxic or produce no therapeutic benefit at all, to minimize drug degradation and loss, to prevent harmful side-effects and to increase drug bioavailability and the fraction of the drug accumulated in the required zone, various drug delivery and drug targeting systems are currently under development Novel drug delivery system is a new approach to drug delivery, In novel drug delivery technology; control of the distribution of drug is achieved by incorporating the drug in carrier system or in changing the structure of the drug at molecular level, novel drug delivery systems possess following advantage, enhancement of solubility, increased bioavailability, protection from toxicity, enhancement of pharmacological activity, enhancement of stability, • Improved tissue macrophages distribution, sustained delivery, protection from physical and chemical degradation, Herbal formulation means a dosage form consisting of one or more herbs or processed herb(s) in specified quantities to provide specific nutritional, cosmetic benefits, and/or other benefits meant for use to diagnose treat, mitigate diseases of human beings or animals and/or to alter the structure or physiology of human beings or animals, Herbal preparations are obtained by subjecting whole plant, fragmented or cut plants, plants parts to treatments such as extraction, distillation, expression, fractionation, purification, concentration or fermentation. These include comminuted or powdered herbal substances, tinctures, extracts, essential oils, expressed juices and processed exudates, actual amount of the drug may not reach the blood. If the drug doesn’t reach the blood at a minimum level which is known as ‘minimum effective level’ then there will be no therapeutic effect, Modern phytopharmaceutical research can solve the scientific needs such as determination of pharmacokinetics, mechanism of action, site of action, accurate dose required, novel herbal drug delivery system includes different types of formulations such as liposomes, phytosomes, pharmacosomes, niosomes, nanoparticles, microspheres, transferosomes, ethosomes, transdermal drug delivery system and proniosomes, Transdermal delivery system provides the advantage of controlled drug delivery, enhanced bioavailability, reduction in side effects and easy application

Author: Delly Ramadon, Maeliosa T. C. McCrudden, Aaron J. Courtenay & Ryan F. Donnelly

Transdermal drug delivery systems , research topic in pharmaceutical technology area, developed pharmaceutical products in global market, delivery routes, such as oral and parenteral, applications of transdermal technologies, transdermal drug delivery systems and enhancement strategies, development of first-generation transdermal products, drug/vehicle interactions, vesicles and particles, stratum corneum modification, energy-driven methods and stratum corneum bypassing techniques, suitable design and implementation of active stratum corneum bypassing methods, notably microneedle technology, transdermal delivery systems have been shown to deliver both low and high molecular weight drugs, microneedle technology platforms, intradermal delivery of drugs/biotherapeutics and therapeutic drug monitoring, strategy for improving transdermal delivery systems, drug delivery systems, Innovation in drug delivery systems is a key strategy employed to improve the bioavailability of active pharmaceutical ingredients (APIs), oral delivery systems offer benefits , such as dosage form variety, painless ease of administration, convenience, self-administration, high safety, and patient compliance , oral delivery systems have some limitations such as poor drug stability in the gastrointestinal tract and subjection to first pass metabolism. For instance, there is a possibility of drug degradation caused by enzymatic reaction or exposure to the acidic environment in the stomach, solubility issues of drugs in the intestinal fluid and their permeability through the intestinal membrane may act as rate limiting steps in drug absorption, causing low bioavailability these drawbacks are routinely observed in the delivery of peptide or protein-based drugs, as a result, intravenous (IV) injection is designated as one of the most promising delivery system for proteinaceous drugs, as it can achieve up to 100% bioavailability, accurate dosing and hepatic metabolism avoidance, injection can achieve up to 100% bioavailability, accurate dosing and hepatic metabolism avoidance, disadvantages are an invasive delivery method, causing pain, low patient compliance, and sharps waste disposal considerations add significant costs, transdermal drug delivery systems use the skin as the drug administration site, the administered drug is absorbed into the systemic circulation via blood vessels in the skin and then circulates around the body, transdermal drug delivery systems offer some advantages for patients, such as being less invasive (some methods are entirely noninvasive), first-pass metabolism avoidance, ease of application and administration, reduce frequency of administration, used for the delivery of different varieties of drugs, both hydrophilic and hydrophobic compounds, Drug absorption via the skin, application of drug-containing dosage forms onto the skin, drug will be released into the skin, Avoidance of significant pre-systemic metabolism (degradation in gastrointestinal tract (GIT) or by the liver) leading to bioavailability improvement, continuity of drug administration in transdermal patches permits the use of a drug with short biological half-life, possibility of sustained and controlled drug delivery over a prolonged period of time even drugs with narrow therapeutic window, Increased patient acceptance and compliance due to the reduction of dosing frequency , more uniform pharmacokinetic profiles of drugs with minimization of peaks-troughs in plasma-drug concentration, thus reducing the risk of toxic side effects, Ease of dose termination in case of any systemic or local adverse effect, providing an alternative to oral dosing in the circumstances of unconscious or nauseated patients, facilitating noninvasive mode of drug administration by avoiding the risk and inconveniences such as needle phobia associated with parenteral therapy, in spite of many potential advantages, transdermal patches has following limitations, essentiality of molecular weight <500 Da to ensure ease of diffusion across the SC, since solute diffusivity is inversely related to its size, Sufficient aqueous and lipid solubility, a Log P (octanol/water) in between 1 and 3 is required for the permeant to successfully traverse the SC and its underlying aqueous layers for systemic delivery to occur, drugs that require high blood levels cannot be administered as transdermal patches is mostly limited only to potent molecules (oral dose is <10 mg/day) , certain drugs, excipient, or components of transdermal patches may cause skin irritation and sensitization leading to erythema and edema, intra- or inter-personal variability in skin changes its barrier function, drug administration in transdermal patches permits the use of a drug with short biological half-life (2–4 h),

Authors Pegah Nasiri, Ali Malekzadeh Shafaroudi , Mahmood Moosazadeh, Delaram Poorkazemi, Javad Mehrani Sabet

Tooth brushing is a primary method to prevent the onset of oral diseases. Aloe vera is commonly used in dentistry as an herbal alternative due to its anti-inflammatory and anti-microbial actions; recently, it has been used in toothpaste formulations as an active agent, Aloe vera toothpaste can be used as an adjunct agent in toothpaste due to its established effects on improving periodontal problems and reducing different oral cavity micro-organisms. The oral cavity contains 500 – 1000 different types of bacteria, fungi, and occasional viruses, cleaning the oral cavity is an essential method of preserving oral health due to removing microbial plaques and preventing them from accumulating on gingiva, periodontal diseases can affect almost 90% of the population. Several etiologic factors can lead to periodontal diseases, including the accumulation of dental plaques. In addition to periodontal diseases, plaque is a critical factor for the initiation and progression of dental caries, tooth brushing once a day is almost adequate to remove plaques and prevent the onset of gingivitis and caries, however, the average adult population do not adhere to sufficient tooth brushing. Consequently, some compounds, such as chlorhexidine, have been used as mouth rinses or are added to toothpaste as adjunctive to improve the mechanical plaque removal, toothpaste can efficiently deliver therapeutically active agents like fluoride to the surface of the teeth, the success of toothpaste depends on its ability to reduce pathogenic oral microflora, researchers have investigated more appropriate alternatives for traditional dental medicines due to side effects, for instance, the unpleasant taste and staining are the main side effects of chlorhexidine mouthwashes

Author Marianne Ashford

The gastrointestinal tract is complex and many physiological factors affect absorption of drugs as they transit through the tract, physiological factors affecting absorption include the transit of dosage forms through the gastrointestinal tract, environmental factors, such as the pH, enzymes and food within the gastrointestinal tract and disease states of the gastrointestinal tract, barriers to drug absorption include environmental factors, such as pH and enzymes, the mucus and unstirred water layer, the gastrointestinal membrane and pre-systemic metabolism, drugs are absorbed through the gastrointestinal membrane via either transcellular, paraceullular or active transport processes. factors that influence the rate and extent of absorption depend upon the route of administration, absorption will depend on the physiology of the administration site(s) and the membrane barriers present at those site(s) that the drug needs to cross in order to reach the systemic circulation, over 80% of medicines being given by mouth, rate-limiting step, controls the overall rate and extent of appearance of intact drug in the systemic, rate-limiting step will vary from drug to drug. For a drug which has a very poor aqueous solubility, the rate at which it dissolves in the gastrointestinal fluids is often the slowest step and the bioavailability of that drug is said to be dissolution-rate limited. In contrast, for a drug that has a high aqueous solubility, its dissolution will be rapid and the rate at which the drug crosses the gastrointestinal membrane may be the rate-limiting step termed permeability limited, Other potential rate-limiting steps include the rate of drug release from the dosage form (this can be by design, in the case of controlled-release dosage forms), the rate at which the stomach empties the drug into the small intestine, the rate at which the drug is metabolized by enzymes in the intestinal mucosal cells during its passage through them into the mesenteric blood vessels, and the rate of metabolism of drug during its initial passage through the liver, often termed the ‘first-pass’ effect, small intestine is the major site of drug absorption, sustained- or controlled-release drug delivery systems

Author: Jitendra Sainy1, Umesh Atneriya, Jagjiwan lal kori, Rahul Maheshwari

Desoximetasone, Plaque psoriasis; Emulgel; Skin penetration; Skin diseases; Kinetic, Plaque psoriasis, is highly prevalent form of psoriasis and basically an autoimmune disease which is challenging to treat. Being the skin disorder plaque is visible mostly on the skin, which causes red and white plaque of dead skin cell on elbow, knees, scalp, and lower back of body, they are usually unquiet, painful, and can crack and bleed, Desoximetasone, (11?,16?)-9-fluoro-11,21-dihydroxy-16-methylpregna-1,4-diene-3,20-dione (DMS) is a synthetic fluorinated corticosteroid known to exert anti pruritic and anti-inflammatory activity and most frequent medication for the treatment of plaque psoriasis , Despite its use in topical skin formulations, DMS’s low water solubility and short half -life are the major obstacles impeding its therapeutic efficacy, emulgel are novel approach for effectively delivery of drug, depend on combined approaches, when gels and emulsions both are together in same dosage form that formulation is called as emulgel, Emulgel formulation were prepared for several classes of drug such as anti inflammatory drugs, anti fungal agent, anti- viral drugs, anti bacterial drugs, local anesthetic and plaque psoriasis ,therefore, emulgel were currently used as a carrier for delivery of various drugs to the skin, the major components of emulgel are emulsifying agent, gelling agent and oil phase, their concentration significantly affects the bioavailability of drug release from the formulation, the merit of emulgel include easily entrapment of water insoluble drugs into gel base with the help of oil in water emulsion system , which enhance cargo loading capacity, stability, and release of drug at controlled manner, Emulgel contained favorable properties for treatment of plaque psoriasis such as bio-friendly, thixotropic, easily spreadable, greaseless, easily removable, water soluble, skin softness, transparent, non-staining, pleasant appearance and stable, the ability of aloe vera to enhance the penetration power of drug and produce excellent emulsion into an emulgel, Their property of staying in contact with skin was explored to develop a emulgel formulation using aloe vera which would retained long period of time onto the skin and releases drug, spreadability and consistency, DMS emulgel was prepared, which can be significantly reached rate and extent of DMS across the cell membrane in controlled manner with help of aloe vera for prolong period of time in the treatment of plaque psoriasis, key benefit of transdermal delivery is to first bypass metabolism , the significant advantage of topical formulation to minimize the off target effect such as pH variation, empty stomach time, presence of enzyme so that topical formulation was exclude the difficulty and discomfort of endovenous treatment therapy, the present research work was to prepare DMS loaded emulgel for effective permeation using aloe vera

Author: Narsih, Sri Kumalaingsih, Susinggih Wijana , Jalan Aloe Vera High Molecular Polysaccharidesad Yani, Pontianak, Kalimantan Barat.

microencapsulation of natural antioxidant powder from Aloe vera (L.) skin was carried out using 10% maltodextrin, 0.3% tween 80 and drying at 600C; and the product was found to have free radical scavenging activity using DPPH (88.31%), total phenol (34.921%), and ? tocopherol by HPLC (87.789mg/g), The FTIR analysis shows that the functional components in the Aloe vera skin powder were phenol, aromatic, substituted alkenes, aromatic acid halide, aliphatic acid halide, eter R-O-R, Nitro NO2, Keton R-CO-R, vinilidene, carboxylic acid, metilene and OH. SEM analysis showed that drying process by foam mat method resulted in a structure that has the capacity to absorb water easily and can dissolved in cold water. The present findings, especially on the microencapsulation of Aloe vera skin powder will provide a new opportunity to improve the bioactive properties of the phyto-component as antioxidant agent, Aloe vera (L.) skin contained pharmaceutical compound such as antioxidant, making it a potential source of raw materials to be processed into natural antioxidant powder, processing of Aloe vera (L.) skin into natural antioxidant powder requires encapsulation using maltodextrin as protective compound, Free radical scavenging activity The antioxidant activity of Aloe vera (L.) skin powder determined using DPPH assay (%) was 88.31%, which is higher than synthetic antioxidant such as BHT (butylated hydroxytoluene) at 70.5% and ?-tocopherol at 65, The higher level of antioxidant activity observed in the encapsulated Aloe vera (L.) skin powder is probably due to its relative resistant to the effect of the drying temperature and the effect of encapsulation using maltodextrin and tween 80, suggested that the increase in free radical antioxidant could be due to better extractability of antioxidant component and higher level of phenolic content, reported that phytochemicals such as phenolic content, ascorbic acid, tocopherol and pigment also contribute to total antioxidant activity and has a good correlation between the antioxidant activity and its total phenolic compound content.

Author Tafara Jambwa, Alvaro Viljoen and Josias Hamman

develop novel drug delivery systems, Excipients from renewable sources, Aloe vera and Aloe ferox as excipients, physical characteristics, mucoadhesive properties, swelling behaviour and drug release kinetics, immediate-release tablet as dosage form is that drug plasma levels actuate over successive doses, Modification in drug-release rate, such as controlled release, Polymers used in dosage form design can be classified as synthetic polymers, semi-synthetic polymers and polymers of natural origin, Multiple-unit dosage forms, granules, pellets or mini-tablets that can be formulated into a single, hard gelatin capsule, aloe leaf materials are suitable as excipients in the design and development of matrix-type tablets for modi?ed drug release

Author: Sun-A Im1, , Young-Ran Lee1, Young-Hee Lee1, Myung-Koo Lee1, Young In Park2, Sungwon Lee3, Kyungjae Kim3 and Chong-Kil Lee1

in vitro cell culture systems, immunomodulatory activity in vivo, route of administration was intraperitoneal or intramuscular, in vivo immunomodulatory, evidence for the immunomodulatory activity of orally administered Aloe vera gel, immunomodulatory polysaccharides, such as acetylated mannan, glucomannan, galactogalacturan, Acemannan, a mixture of various length polymer chains of ?-(1,4)-linked acetylated galactomannan isolated from Aloe vera, may be the best-characterized immunomodulatory polysaccharides, acemannan completely cured or significantly reduced the tumor burden, Acemannan is also effective in the treatment of spontaneously developed canine and feline fibrosarcoma, immunoaugmenting activities of acemannan are mediated through the activation of macrophages, Acemannan activates macrophages to produce inflammatory cytokines such as IL-6 and TNF-a, increase NO production by macrophages, upregulate the phagocytic and candidicidal activities of macrophages, Acemannan also augments hematopoiesis, induces maturation of immature dendritic cells, healthcare products, immunomodulatory activity of Aloe components in in vitro cell culture systems, polysaccharides isolated from cellulose-treated, molecular size-activity relationship studies, optimal molecular size for maximum immunomodulatory activity, between 5 kDa and 400 kDa; polysaccharides smaller than 5 kDa or larger than 400 kDa exhibited only marginal immunomodulatory activity, HPLC analysis, Aloe vera gel exert immunomodulatory activity in vivo as well as in vitro, acemannan, the major polysaccharide present in Aloe vera gel, mediates its activity mainly through activation of macrophages

Author: W. Gerber, D. Steyn, Awie Kotzé, H. Svitina, C. Weldon, J. Hamman

nasal route of drug administration offers an alternative way for oral drug delivery and has the benefit of avoiding first-pass metabolism through drug delivery directly into the systemic circulation, drug absorption enhancing effects of selected aloe, Pharmacokinetic modulation, drug-herb interactions, Substances responsible for the enhancement of pharmacokinetic profiles (i.e. bioenhancers) may be substrates, inhibitors and/or inducers of absorption, metabolism, distribution and excretion, co-administered drug bioavailability, applicable to drugs with unfavourable physico-chemical properties such as large molecular weight drugs that experience difficulty to diffuse across biological membranes, as well as drugs that exhibit a high affinity for efflux transporters or metabolic enzymes, drug membrane permeation enhancing effects are Aloe vera, Aloe Vera Gel have the ability to open tight junctions between adjacent epithelial cells and thereby increase drug permeation across the intestinal epithelium, buccal epithelium and the skin, nasal route of drug administration facilitate delivery of poorly bioavailable drugs, nasal administration, drugs are delivered directly into the systemic circulation, thereby circumventing first-pass metabolism, when grown under ALI conditions, the RPMI 2650 cell line presents as a uniform multi-layered cell formation that expresses tight-junctions, multi-drug resistance proteins and transepithelial resistance and permeability values similar to that of excised human nasal mucosa, Aloe Vera Gel gel increased the transport of different molecules in a concentration dependent manner across other epithelial membranes including intestinal and buccal mucosal surfaces, functional excipients and/or bioenhancers,

Author: Tewolde Mulu, Firomsa Teshale, Samuel Gemeda, Omprakash Sahu.

complex sugars, mucopolysaccharides, carbohydrates ,  therapeutic values, gastro-protective effect, structure and proper function and absorption of the digestive tract, capacity to stimulate the immune system , aloe vera  has special properties as a skin care product and as raw material for the manufacturing of high grade nutritional, medicinal and cosmetic products, acilitates digestion, blood and lymphatic circulation and functioning of kidney, liver and gall bladder, in care product, providing antifungal, antibacterial and antiviral activity. Aloe Vera has the ability to provide essential nutrients, kill bacteria, viruses, fungi, yeasts and reduce inflammation. Aloe Vera can also reduce inflammation to injured tissue

Author Rinda Gita Atikasari, Diah Adriani Malik, Retno Indar Widayati, Puguh Riyanto, Asih Budiastuti, Muslimin and Hardian

For toddlers younger than 36 months, most of them still use diapers, so diaper rashes frequently appear in the diaper area. To improve the skin barrier, a moisturizer is needed to repair the skin barrier, made with aloe vera as moisturizer for diaper dermatitis, topical ingredients with natural ingredients can be used, prove the effectiveness of topical Aloe vera moisturizer compared to other topical ingredients against diaper dermatitis, decrease in the degree dermatitis diaper after treatment with Aloe vera, results of qualitative analysis on other skin barrier function parameters indicate that topical Aloe vera can improve skin barrier function in diaper dermatitis patients

Author: Ranade A, Ranpise NS, Ramesh C.

treatment for Helicobacter pylori?induced peptic ulcer includes a 14?day “triple therapy” of two antibiotics and a proton pump inhibitor. However, the current therapy has side?effects like stomach upset, non?compliance, incomplete absorption of drug and antibiotic resistance, best possible alternative is to deliver herbal constituents, present investigation is designed to deliver and retain two herbal constituents in the stomach for better action against gastric ulcers. The objective was to develop a bilayer floating tablet of monoammonium glycerrhizin and Aloe vera gel powder through rational combination of excipients to give the lowest possible lag time with maximum drug release in 7 h. Formulation OF2 containing hydroxy propyl methyl cellulose E5, rospovidone and effervescent agents in the ratio 1:2 gave 98% drug release with desired floating properties. Pharmacodynamic studies in rats showed that the combination of monoammonium glycerrhizin and Aloe vera gave 99% ulcer inhibition in comparison with 51% ulcer inhibition in the group administered with monoammonium glycerrhizin alone. X?ray studies in rabbits proved the gastroretention of the tablet for more than 6 h, this suggests relevance of NDDS in delivery of herbal constituents in the treatment of gastric ulcer, Aloe vera gel showed inhibition of gastric acid secretions by direct interaction with the acid-producing cells or possible interaction with H2 receptors on the parietal cells, the antiulcer activity is due to its anti-inflammatory, cytoprotective, healing and mucus-stimulatory effects, the gastroprotective activity of Aloe vera at lower concentrations is due to the presence of lectins. Lectins are proteins/ glycoproteins capable of binding to carbohydrate moieties

Author E.. Pretorius, C. Willers, J. Hamman, J. D. Steyn

oral administration route is still the most preferred by patients for drug treatment, but is unfortunately not suitable for all drug compounds, protein and peptide drugs (e.g. insulin) are usually administered by injection since they are unstable in the gastrointestinal luminal environment and have poor membrane permeation properties, functional excipients such as drug absorption enhancers can be co-administered, Aloe vera gel has shown the ability to improve the permeation of drugs across the intestinal epithelium, insulin permeation enhancing effects of Aloe Vera Gel gel material across excised pig intestinal tissues from different regions of the gastrointestinal tract and to identify the gastrointestinal region where the highest insulin permeation enhancement was achieved, Insulin transport across excised pig intestinal tissues from the duodenum, proximal jejunum, medial jejunum, distal jejunum, ileum and colon was measured in the absence and presence of Aloe Vera Gel gel (0.5% w/v) using both the Sweetana-Grass diffusion chamber and everted sac techniques, gastrointestinal permeation enhancing effects of Aloe Vera Gel gel on insulin is region specific with the highest effect observed in the ileum and colon

Author A Yagi

aloe high molecular fractions (ALOE VERA HIGH MOLECULAR POLYSACCHARIDES) were obtained in original and natural form containing less than 10 ppm of barbaloin. ALOE VERA HIGH MOLECULAR POLYSACCHARIDES mainly contained high molecular fractions, such as polysaccharide (acemannan) and glycoprotein (verectin) showing immunomodulatory and anti-inflammatory activities. On the basis of chemical and biochemical properties, ALOE VERA HIGH MOLECULAR POLYSACCHARIDES were examined for the therapy designed by the implementation of well-controlled clinical trials, and exhibited the efficacy as immunomodulators for viral infection-induced hepatic periportal fibrosis and type 2 diabetic patients, and as wound and ulcer-healing ointment to patients suffering from bedsore. Therefore, ALOE VERA HIGH MOLECULAR POLYSACCHARIDES were considered to be a novel low-cost and safe drug of natural origin, indicating a possible therapeutic efficacy in prevention of age-related diseases, Aloe vera high molecular weight fractions; Therapeutic efficacy; Hepatic periportal fibrosis; Type 2 diabetes; Bedsores, Aloe polysaccharides High Molecular containing less than 10 ppm of barbaloin, polysaccharide (molecular weight 1×106 D) and glycoprotein, verectin (molecular weight: 29×103 D), were prepared by patented hyper-dry system in combination of freeze-dry technique with micro wave and far infra-red radiation. Aloe polysaccharides High Molecular produced significant decrease in blood glucose level sustained for 6 weeks of the start of the study. Significant decrease in triglycerides was only observed 4 weeks after treatment and continued thereafter. No deteriorate effects on kidney and liver functions were apparent, treatment of diabetic patients with Aloe polysaccharides High Molecular may relief vascular complications probably via activation of immune system, Oral supplementation with Aloe polysaccharides High Molecular could be helpful in alleviating the fibrosis and inflammation of hepatic fibrosis patients, efficacy of the preclinical trials for bedsores by the external use of Aloe polysaccharides High Molecular ointment, adjuvant properties of a poly dispersed ?-(1-4) linked acetylated mannan (ACE-M) were evaluated by Chinnah, et al[4] showing that ACE-M has the effect on flock immunity to Newcastle disease virus and infectious bursal disease virus. Acemannan also stimulated the adjuvant activity due to its capacity to promote differentiation of immature dendritic cells[5]. Intranasal immunization using HBsAg-acemannan formulations demonstrated the enhancement of the immune responses to nasally administrated hepatitis B surface antigen, generating IgG antibody-titers in high level in mice serum[6]. Acemannan was able effectively and durably to increase the activity of macrophages from the systemic immune compartment in chicken, especially nitrogen oxide (NO) production, Also human clinical data demonstrating increased bioavailability of vitamins C and E when taken in combination with aloe vera gel powders were presented, Aloe vera gel products improved the absorptions of vitamins C and E as an adjunct and arginine as a precursor of NO for people who take vitamins and amino acids supplements, he Japanese have higher rate of life expectancy and that Japan is rapidly becoming a super aging society. Almost 5 per cent of the aged, who develop diseases such as cerebro-vascular related disorders, mental problems, fractures, cancer and infections, also end up suffering from bedsores. It has been found that patients often opt for treatment, when the bedsores become very severe and adding more complications in their treatment. It may be presumed that prevention and early detection are vital for the treatment of bed sores. In our present study, we have tested herbal formulations having Aloe vera gel powder for its efficacy and activity on bedsores.