Percutaneous absorption of a new antiandrogen included in liposomes or in solution

The percutaneous absorption and the cutaneous distribution of a new antiandrogen, RU 58841, 0.5% in liposomes or in solution were compared after topical application. In vitro percutaneous absorption experiments were performed on human dermatomed skin with Franz diffusion cells. In vivo cutaneous distribution after application on the skin of hairless rat was studied with the method previously described by Schaefer and Stuttgen. The in vitro experiments showed that liposomes considerably reduce the RU 58841 percutaneous absorption compared to solution. After in vivo application, drug content of skin surface, stratum corneum, epidermis and dermis were measured, it demonstrated a slower permeation of the drug and a longer duration in the epidermis and dermis for the liposomes compared with the solution. The distribution profile of solution presented an RU 58841 concentration gradient decreasing from the surface to the deeper layers while an RU 58841 concentration increase between 30 and 150 mu m in depth was observed with liposomes showing an accumulation in the sebaceous structures. In conclusion, there is a trend towards a more favourable topical application of liposomes for local effects. They reduce percutaneous absorption, increase accumulation and retention of the drug in the dermis and produce a targeting in the sebaceous structures.