In vitro human topical bioactive drug transdermal absorption: estradiol.

Use of the percutaneous route may avoid some of the undesirable side effects that occur following oral administration in estrogen replacement therapy. At present, knowledge of estradiol transdermal properties relating to delivery of drugs in the skin is lacking. One reason is that in the existing transport models of estradiol, the skin is regarded as a single layer. This study revealed a significant difference of effects on estradiol delivery in the 3 sublayers of the skin and has caused us to believe that if we can obtain information about the transfer properties of estradiol in human skin (3 sublayers), we will not only increase our understanding of the estradiol biotransport mechanism, but also benefit clinical application. Accordingly, radioactive 17beta-estradiol was used to clarify the percutaneous absorption of estradiol into the 3 sublayers of the skin (stratum corneum, epidermis, and dermis) and to evaluate the effect of drugs delivered in each sublayer. Based on data thereby obtained, mathematical models were built to further obtain transport parameters (diffusivity, permeability, lag time, and partition coefficients) for the 3 layers of the skin.