ABSTRACT
INTRODUCTION As the largest organ of the human body, the skin provides an exceptional heterogeneous interface to protect the internal organs from various physical and chemical environmental insults by functioning as a physical, metabolic, and anti-UV barrier. It is well documented in the percutaneous penetration literature that the tightly packed lipid bilayer of the stratum corneum is efficacious in preventing exogenous compounds from entering the body (1). Most of the work done on the skin barrier focuses on the stratum corneum’s physical barrier property. However, the skin should not only be thought of as an inert barrier. It is also a chemically active barrier, with enzymes located in the viable epidermis (2) as well as in the extracellular spaces of the stratum corneum (3-5) and the dermis, in which the primary sites of metabolism are the skin appendages (2). Cutaneous transport proteins expressed in skin constitute a second part of the chemical barrier function of the skin. Keratinocytes are the sites of expression of these proteins, which can act as substrates for a variety of topically applied compounds. In this brief review we focus on the possible therapeutic and adverse effects that cutaneous enzymes and transporters have on drug penetration into the skin. We also focus on the predictive role of mathematical models in understanding cutaneous biotransformation.
