Controlled drug release from a novel liposomal delivery system. II. Transdermal delivery characteristics

Recently, we reported the evaluation of a prototypal liposomal delivery system, which consisted of a thin agarose gel throughout which a model drug progesterone (PG), associated with multilamellar liposomes, was dispersed. The device was able to: (1) release PG into aqueous buffer solution with essentially zero-order kinetics for at least 24 hours, and (2) modulate PG delivery across hairless mouse skin in vitro. In this paper, we describe further research which examines the influence of lipid formulation on the transdermal delivery of PG from this system. Significant effects on the transdermal delivery of PG by the lipids employed were observed, despite similarities in the release behavior of different formulations into aqueous buffer. For example, transdermal delivery of PG from systems formulated with saturated acyi chain phospholipids (i.e. DMPC and DPPC) was an order of magnitude slower than that from cis-unsaturated phospholipid formulations (i.e. EPC and DOPC). The addition of a cis-unsaturated fatty acid to saturated acyl chain liposome devices increased the delivery rate of PG an order of magnitude. The results suggest the effective co-delivery of drug plus penetration enhancer under both serendipitous and deliberate circumstances.