Model studies of epidermal permeability

An in vitro physical model approach for describing and predicting transport of molecules and ions across skin is examined. The proposed model is represented by two transport-resistant layers in series: the stratum corneum and the epidermis plus dermis. The stratum corneum is regarded as the principal barrier to transport and is composed of two parallel pathways: the lipoidal pathway and the pore pathway. The epidermis-dermis is treated as a porous membrane. The model predicts three regimes for the transport behavior of permeants, and these predictions have been compared with experimental permeability coefficient data obtained with hairless mouse skin in a two-chamber (aqueous) diffusion cell. The model predicts (1) that extremely lipophilic molecules are rate-limited by the epidermis-dermis and have a limiting permeability coefficient value; (2) that extremely polar permeants are rate-limited by the pore pathway of the stratum corneum with its limiting permeability coefficient; and (3) that permeants with intermediate polarity are transported via the lipoidal pathway and exhibit a lipophilicity-dependent permeability coefficient. Experimental data involving a large number of permeants are found to be consistent with these model predictions. The model approach also has been applied in the study of the mechanism(s) of skin transport enhancement induced by short-chain alkanols in aqueous media. A possible mode of enhancing the lipoidal pathway at low concentrations of the alkanols may involve the polar head region of the lipid bilayer or the region slightly below the polar head plane, or both; alkanols may solvate the lipid-water interface, intercalating and disrupting the interactions of the upper regions of the alkyl chains and the interactions between the polar head groups. This could result in an increase in both diffusivity and partitioning tendency for a permeant in this microenvironment. At higher alkanol concentrations, the pore pathway becomes dominant in controlling the transport of the permeants across the stratum corneum.