SITE-SPECIFIC DRUG-DELIVERY TO PILOSEBACEOUS STRUCTURES USING POLYMERIC MICROSPHERES

In order to improve the therapeutic index of adapalene, a new drug und er development for the treatment of acne, site-specific delivery to th e hair follicles using 50:50 poly(DL-lactic-co-glycolic acid) microsph eres as particulate carriers was investigated in vitro and in vivo. Th e percutaneous penetration pathway of the microspheres was shown to be dependent on their mean diameter. Thus, after topical application ont o hairless rat or human skin, adapalene-loaded microspheres (5-mum dia meter) were specifically targeted to the follicular ducts and did not penetrate via the stratum corneum. The in vitro release of adapalene f rom the microspheres into artificial sebum at 37-degrees-C was control led and faster than the in vivo sebum excretion in humans. Aiming to r educe either the applied dose of drug or the frequency of administrati on, different formulations of adapalene-loaded microspheres were evalu ated in vivo in the rhino mouse model. A dose-related comedolytic acti vity of topical formulations of adapalene-loaded microspheres was obse rved in this model. Furthermore, by applying a site-specific drug deli very system (0.1% adapalene) every other day or by administering a 10- fold less concentrated targeted formulation (0.01%) every day, a pharm acological activity equivalent to a daily application of an aqueous ge l containing drug crystals (0.1% adapalene) was observed. Since an aqu eous gel containing 10% adapalene-loaded microspheres was not irritati ng in a rabbit skin irritancy test, this formulation was applied onto forearms of human volunteers. Site-specific drug delivery was further evidenced by follicular biopsy. These results support the view that fo llicular drug targeting using 5-mum polymeric microspheres may represe nt a promising therapeutic approach for the treatment of pathologies a ssociated with pilosebaceous units.