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Role of transepidermal and transfollicular routes in percutaneous absorption of steroids: in vitro studies on human skin.

Percutaneous absorption theoretically comprises two components: the transepidermal and the transfollicular routes. The aim of the present work was to confirm this hypothesis in the human skin by comparing the in vitro percutaneous absorption of four steroids through scar skin without hair follicles and sebaceous glands and through normal adjacent skin from abdominal or mammary plasties. In all cases, the absorption of the four steroids was significantly higher in normal skin than in scar skin. The cumulative percentages of progesterone and testosterone after 8 h of application were, respectively, 3.1- and 2.4-fold higher in normal skin than in scar skin. After 24 h of application, the cumulative percentages of estradiol and hydrocortisone were 1.7- and 2.4-fold higher in normal skin than in scar skin. At the end of the experiments, the quantities of drugs remaining in the skin after 8 or 24 h of application were the same in normal skin and in scar skin except for progesterone for which they were 2-fold greater in normal than in scar skin. In each case, a histological characterization of the scar skin was made in comparison with the normal adjacent skin. The main modifications observed on scar skin were the following: absence of hair follicles and sebaceous glands, thinning of the collagenous fibers with parallel orientation to the dermoepidermal junction and decrease in the number or disappearance of the elastic fibers. These experiments confirmed that human skin appendages, hair follicles and sebaceous glands, constitute a route of penetration for steroids and thus probably for other chemicals of similar molecular weight and properties.