Follicular Delivery

Lieb et al. (175,176) proposed that liposomes may be useful for targeting drugs to skin follicles for the treatment of diseases, such as acne and alopecia. Their initial experiments, using the hamster ear pilosebaceous unit, demonstrated that carboxy-fluorescein, incorporated into phospholipid liposomes, was more efficiently targeted to follicles than when formulated as a simple aqueous solution, a propylene glycol (5%) solution, or a sodium dodecyl sulfate (0.05%) solution (175). However, most of the carboxyfluorescein was located in the epidermis. In later experiments, application of cimetidine, incorporated in phospholipid and nonionic liposomes, was compared with its application in a 50% alcohol solution (176), and generated data that was similarly equivocal. In this case, although small amounts of drug were located within the pilosebaceous unit, most was located on the surface or within the stratum corneum (determined by tape-stripping). Nonetheless, the data showed that the li-posomal formulations were considerably more effective at delivering the drug to the stratum corneum and the follicles than was the alcoholic solution. Interestingly, the phospholipid liposomes delivered approximately twice as much drug to these compartments as the nonionic liposomes.

More recently, this group has demonstrated that nonionic liposomes were capable of delivering the macromolecules cyclosporine and interferon-alfa into pilo-sebaceous units (177). Three nonionic and one phospholipid liposome were evaluated. The most effective vesicle comprised glyceryl dilaurate (57% by weight), cholesterol (12%), and polyoxyethylene(10)stearyl ether (28%), which facilitated the follicular deposition of both hydrophilic and hydrophobic drugs. The authors speculated that the low-melting point of glyceryl dilaurate (30°C) may have resulted in fluidization of the liposome bilayers following application of the formulation, and this led to partial release of polyoxyethylene(10)stearyl ether (a known skin penetration enhancer) (165), which further led to an enhancement of drug deposition. Given these studies, the authors investigated the liposomal delivery of plasmid DNA to the skin (178). Their results suggested that nonionic--cationic liposomes (comprising glyceryl dilaurate, cholesterol polyoxyethylene(10)stearyl ether, and 1,2-di-oleoyloxy-3-(trimethylammonio)-propane) could deliver expression plasmid DNA to perifollicular cells and mediate transient transfection in vivo. These data show promise for future topical gene therapy for a number of dermatological diseases caused by abnormal regulation of soluble cytokines.

Other recent data on liposome-mediated drug delivery to follicular regions has been contradictory. Whereas, Bernard et al. (179) demonstrated that phospholipid liposomes were useful for targeting delivery of an antiandrogen to the sebaceous gland, Tshan et al. (180) found no enhancement of follicular deposition of isotretinoin when applied in liposomal formulation. Overall, the number and variety of constituents from which lipid vesicles have been constructed, the large number of permeants and formulations studied, and the diversity of experimental methods render it difficult to establish any systematic ground rules. It is clear, however, that although there is considerable evidence for improved drug delivery characteristics, much remains to be achieved in this field.

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