O#07   Selective Hair Follicle Targeting

Lingna Li, Normitsu Saito, Ming Zhao, Robert M. Hoffman. Anti Cancer, Inc., San Diego, CA, USA

There is a need for targeting selective, effective agents to the pilosebaceous unit. We have demonstrated that the 5a-reductase inhibitor N,N-diethyl-4-methyl-3-oxo-4-aza-5a-androstane-17b-carboxamide (4-MA) incorporated into liposomes induces apoptosis and inhibits growth of the dihydrotestosterone (DHT)-dependent hamster flank organ sebaceous gland upon topical application. We have compared topical application of liposome 4-MA and solvent-formulated 4-MA and observed selective efficacy of topical application of liposome 4-MA by the reduction of size and induction of apoptosis only in the treated hamster flank organ. Apoptosis induced by liposome 4-MA in the treated flank organ sebaceous gland cells was observed both by assays for DNA fragments (TUNEL) and by observation of condensed and fragmented nuclei. When 4-MA was topically applied formulated in ethanol and glycerol, the selective efficacy was lost. Liposome 4-MA did not significantly affect prostate weight, T/DHT ratios or body weight gain compared to controls indicating safety as well as efficacy of topical application of liposome 4-MA for acne and other hair follicle disorders. A novel gene therapy technology of hair follicles has been developed which results in efficient alteration of the hair shaft phenotype. High-level transgene expression was maintained in vivo in hair follicles sufficiently such that growing hair shafts were phenotypically altered. Mouse anagen skin fragments in histoculture were transduced at high efficiency by adenoviral-green fluorescent protein (GFP) with subsequent grafting of the skin fragments to nude mice. The histocultured skin fragments were treated with collagenase which made hair follicles accessible to the adenoviral-GFP gene allowing high-efficiency transduction. After transplantation of the GFP-transduced skin to nude mice, GFP was readily visualized in as many as 75% of hair follicles including large numbers of GFP-fluorescent growing hair shafts. This novel technology has allowed, for the first time, efficient genetic modification of the hair shaft. Future studies will utilize this technology for delivery of therapeutic genes to the hair follicle.