Determination of penetration enhancer utilities and mechanisms of action in models of skin and keratinized oral mucosa.

摘要

Few drugs are suitable for transdermal or oral mucosal delivery, since both skin and oral epithelia function as barriers to absorption of foreign materials. One method to render membranes more permeable to drug molecules involves utilization of a chemical penetration enhancer to reversibly reduce membrane barrier function without permanently damaging viable cells. An understanding of the utility and mechanisms of enhancement is important both in evaluating the commercial potential of an enhancer and in optimizing formulations containing that enhancer. In the current studies, the utilities of several lipophilic penetration enhancers were compared in models of skin and keratinized oral mucosa. Furthermore, the mechanisms of action of these and other lipophilic enhancers were investigated, with particular emphasis on enhancer-membrane lipid interactions.; Diffusion profiles for a lipophilic and a hydrophilic model compound varied depending on the drug, enhancer, and membrane investigated. Therefore, despite structural and functional similarities between skin and keratinized oral mucosa, the selection of an appropriate chemical penetration enhancer could in fact depend on the both the intended route of drug delivery as well as physicochemical properties of the drug to be delivered. Membrane lipid extraction was observed following enhancer application to a skin model. Furthermore, membrane lipid fluidization and a decrease in the cooperativity of acyl chain melting were observed following addition of enhancers to a model lipid system. Therefore, it appears that these enhancers may act via one or more of these mechanisms.