Solvent-mediated alterations of the stratum corneum

Abstract

The intercellular lipid multilayers of stratum corneum, the outermost layer of mammalian skin, are generally accepted as the rate-determining pathway of transmembrane diffusion for lipophilic solutes. The effects of a series of saturated and unsaturated octadecanoic acids (saturated stearic acid, cis- and trans-octadecenoic acid) and a series of short-chain alcohols (ethanol, n-propanol, isopropanol and n-butanol) on the thermotropic phase behavior of stratum corneum have been investigated. In conjunction with the thermotropic phase behavior, fatty-acid-induced effects on the permeation of a lipophilic compound have also been studied. The alcohol-induced effects were determined at concentrations that haue given penetration enhancement for the respective alcohols in order to relate the findings to available skin transport data from literature. Permeation enhancement of lipophilic solutes does not necessarily occur with a concomitant decrease in the gel to liquid-crystalline phase transition. The unsaturated fatty acids in the presence of aqueous ethanol solutions have been associated with conformational alterations of the gel phase lipid domain. However, the effect of fatty acids is complicated by the presence of the cosolvent. Therefore, the thermotropic phase behavior of the stratum corneum was also investigated in the presence of a series of short-chain alcohols. Short-chain alcohol enhanced permeation may result from a reduction of lipid polar head interactions, an inter facial transport pathway between limited populations of interdigitated and noninterdigitated gel phases within the membrane or further disordering of possible liquid-crystalline phases within the membrane.