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
