In the past decade, liposomal formulations have been extensively employed to enhance the efficiency of drug delivery via several routes of administration. In a number of instances, liposomal drug formulations have been shown to be markedly superior to conventional dosage forms, especially for intravenous and topical

No abstract

This review will highlight work done in our laboratories evaluating topical liposomal delivery in a wide variety of animal models and human skin using both in vivo and in vitro techniques. The mechanism by which liposomes facilitate deposition of drugs into the skin and some potential applications of topically applied liposomes will be discussed. Particular emphasis will be placed on the development of analytical techniques that allow the quantification of drug levels in the various skin strata and in pilosebaceous structures. Appropriate models of skin representing the two cases, as well as those wherein both routes are available for skin deposition, were examined using a wide variety of liposomal preparations containing radiolabeled and fluorescent molecules as marker compounds.

The extent of uptake of gamma interferon (gamma-IFN) in various strata of hairless mouse, human and hamster skin upon application of a liposomal formulation and an aqueous solution were determined by in vitro diffusion cell experiments. For each of the animal species studied, 70-80% of the liposomally entrapped IFN was deposited onto or penetrated into the skin as determined 24 h after in vitro application. However, a significant fraction of this total amount (approximately 0.25-0.30) is either adsorbed to or associated with the stratum corneum. The drug content found in the deeper skin strata, where the receptor sites reside, suggests that drug deposition is strongly influenced by the skin species tested. The percent of applied drug found in this strata 24 h after application followed the order: hamster (6.1) much greater than human (0.9) greater than hairless mouse (0.3), although the amounts of drug in the total skin of each species tested were approximately the same. This indicates that the deposition of drug into the living epidermis and/or dermis cannot be predicted by determination of the amount of drug in the total skin. The amounts in the deeper skin strata were also in the order of increasing number of follicles/hair in the skin species, suggesting that the transfollicular route is an important pathway for liposomal topical therapeutics.

The topical delivery of several liposomal interferon formulations was evaluated by in vitro diffusion experiments in an effort to understand the effects of liposomal composition and method of preparation on the deposition of interferon into the stratum corneum and deeper strata of the skin. Application of liposomes prepared from lipids with a composition similar to that of the stratum corneum resulted in almost twice the amount of interferon being deposited in the deeper skin layers than did application of liposomes prepared from phospholipids. Topical application of "skin lipid" liposomes prepared by the dehydration-rehydration method was twice as effective as was topical application of liposomes prepared by the reverse-phase evaporation method with respect to their ability to deposit interferon into the skin strata where the basal cell layers reside. These results are consistent with the effects of liposomal composition and method of preparation on the ability of the formulation to reduce lesion scores in the cutaneous herpes simplex virus type 1 guinea pig model.Genital herpes is currently an epidemic sexually transmitted disease. The successful treatment of cutaneous virus infections with interferon (IFN) depends on the ability to effectively deliver IFN to the infected cells. So far it has proven impossible to obtain adequate tissue levels to control herpes and other skin viruses by conventional avenues of drug administration. Systemic regimens adequate to suppress skin symptomology often result in adverse systemic effects and still may not overcome the inaccessibility of the target tissue to the drug. In these regards, drug delivery remains the most limiting factor to the effective treatment of herpes.We recently reported that topical application of liposomally entrapped IFN caused a reduction of lesion scores in the cutaneous herpes simplex virus type 1 guinea pig model, whereas application of IFN formulated as a solution or as an emulsion was ineffective (9). For phospholipid-based liposomes, the method of preparation rather than the lipid composition of the bilayers appeared to be the most important factor for reducing lesion scores. We also showed that greater efficacy was observed when IFN was entrapped in liposomes prepared from lipids with a composition similar to that of the stratum corneum rather than from phospholipids.