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.
