Reduction of the Skin Permeation of Xenobiotics Using Chemical Penetration Retarders

Abstract

The permeability characteristics of human skin have been reasonably well established and have been extensively reviewed elsewhere (Barry, 1983; Wester and Maibach, 1992). Briefly, the barrier function of skin is the result of the distribution of intercellular lamellar lipids within the stratum corneum. These lipids, which are secreted from the corneocytes during the differentiation process, mainly comprise ceramides, fatty acids, cholesterol and cholesterol derivatives. There are several bilayer arrangements between each individual corneocyte and, at the lamellar lipid-corneocyte interface, there appears to be a unique attachment of ceramide molecules to the glutamate side chains of membrane proteins (Downing, 1992). Although the precise arrangement of the lipids within the stratum corneum intercellular bilayers is not yet established, the relative rigidity of the structures indicates that cholesterol and its derivatives play a major role in the structural matrix (Brain and Walters, 1993). The stratum corneum, therefore, presents a considerable lipophilic barrier to the permeation of chemicals.