(128c) Skin Enzymes Distribution in Transdermal Drug Delivery

Skin has two barriers for protective functions; a physical barrier of stratum corneum and a biochemical barrier in epidermis and dermis. Skin enzymes biotransform not only chemical toxins and tumorogens but also drugs entering from the skin surface. Pharmacokinetics in the skin, the penetration flux and distribution of the drug and its metabolite, is influenced by the distribution of metabolic enzymes in the skin. Thus, knowledge of enzymatic activities and distribution is important for developing safe and efficacious transdermal drug delivery. In this study, we investigated the skin distribution and enzymatic activity of enzymes (hydrolase, oxidase, and reductase) in human and animal skin in vitro. In human cadaver skin, skin enzymes distribution has a peak value at 80-120 µm of the distance from skin surface which is correspond to the layer just before capillary vessel. This result shows that skin enzymes effectively metabolize drugs before entering the systemic circulation. On the other hand, enzyme distribution in animal skin is different from human skin. Therefore, the biological barrier has a different distribution among species.