EPIDERMAL ENZYMES AS PENETRATION ENHANCERS IN TRANSDERMAL DRUG-DELIVERY

Epidermal enzymes play an important role in the process of differentia tion of keratinocytes. The present preliminary in vitro study was unde rtaken to observe if topical enzyme treatment influenced permeation of compounds across the skin. Due to the noted function and importance o f phosphatidylcholine metabolism during maturation of the barrier lipi ds, the effects of topical application of the phosphatidylcholine depe ndent phospholipase C enzyme (not present in epidermis) on skin penetr ation of three model drugs, viz, benzoic acid, mannitol and testostero ne, were studied. Similar studies were also carried out using epiderma l enzymes like triacylglycerol hydrolase, acid phosphatase, and phosph olipase A(2) (present in epidermis). Pretreatment of skin with phospho lipase C significantly enhanced permeation of benzoic acid, mannitol, and testosterone relative to untreated skin. Triacylglycerol hydrolase (neutral) increased the penetration of mannitol 3-fold and had no eff ect on benzoic acid penetration. Topical application of acid phosphata se did not alter the permeation of any of these compounds. Phospholipa se A(2) significantly enhanced permeation of benzoic acid and mannitol while it did not have any effect on the penetration of testosterone. These results for the first time demonstrate that enzymes may remarkab ly affect and/or regulate the permeation of topically applied compound s.