TRANSDERMAL ABSORPTION OF STEROIDS

The transport mechanisms of selected steroids in the presence of a series of aqueous ethanol solutions have been probed in vitro using hairless mouse and human tissue, as well as in vivo using the unique human skin sandwich flap model. Permeation and biophysical studies have also been performed under similar conditions in order to elucidate the biophysical alterations in hairless mouse and human stratum corneum induced by the vehicle solutions that contribute to the percutaneous transport mechanisms of steroids. Progesterone, estradiol and hydrocortisone transport across hairless mouse skin under the same conditions was examined to explore the effects of permeant properties. Steroid uptake and in vitro permeability coefficients across both skin species decreased with decreasing steroid lipophilicity. The polar character of the steroids influences not only partitioning, but also the effective diffusivity in the stratum corneum, as suggested from permeability coefficients calculated with a mathematical model. As steroids become more polar, the effective diffusivities decrease and the degree to which the stratum corneum controls overall diffusion increases. Estradiol permeability coefficients in vivo with the human skin sandwich flap were 10-fold higher than with human epidermis in vitro. Estradiol uptake and permeability coefficients decreased with the presence of increasing ethanol concentrations. Similarities in estradiol permeation in vitro through hairless mouse skin and human epidermis were further reflected in similarities of the human and hairless mouse stratum corneum lipid domain biophysical structures.