Skin penetration

Abstract

Penetration of the skin is a key element in cutaneous reactions to xenobiotics, drugs, or other compounds. The structure of the skin is described in the present chapter. Based on this structure analysis, theoretical diffusion models are presented. The inter- and intraindividual variation in the skin-barrier function is discussed and the complex influence of a carrier medium on percutaneous absorption is demonstrated. The different penetration pathways through which topically applied substances can pass the skin barrier are described. While in the past, it was assumed that topically applied substances penetrate by the intercellular route, in recent studies, it was demonstrated that the hair follicles can also represent an efficient penetration pathway and a long-term reservoir. The skin contains a wide range of enzymatic activities, including phase-I oxidative, reductive, hydrolytic, and phase-II conjugative reactions, as well as a full complement of metabolizing enzymes. It is demonstrated that the metabolic activity is a primary consideration in the design of prodrugs and may influence the bioavailability of drugs delivered via dermatological or transdermal formulations. The influence of pathological processes on the skin barrier is demonstrated. Reduced skin-barrier function can be observed for a number of pathological conditions including ichthyosis, psoriasis, atopic dermatitis, and contact dermatitis. It is generally accepted that this can be attributed to structural alterations in the stratum corneum. © 2011 Springer-Verlag Berlin Heidelberg.