Mechanisms of topical delivery of liposomally entrapped drugs

Abstract

Our research on the mechanism by which liposomally entrapped solutes are transported across the skin was prompted by an investigation reported in the literature which con- cluded with meager supporting evidence that liposomes containing triamcinolone acetonide penetrated the stratum corneum intact and, thereby, increased skin absorption. To elucidate the mechanism we used glucose, hydrocortisone, progesterone and multilamellar DPPC liposomes. Experimental strategies involved: DSC determinations, in vivo permeation of hairless mouse skin by liposomes, by liposome-entrapped solutes (15:1) and by solutes in simple solution; and in vitro release kinetics of liposome-entrapped solutes.The liposomes neither penetrated the skin nor fused with the stratum corneum. Progesterone and hydrocortisone, which were intercalated in the bilayer structure, permeated the skin with ease comparable to free drug. The skin transport of the highly polar glucose entrapped in the aqueous regions of the liposome was markedly slow as compared to the free species. Physical model analysis indicated that the slow release rate of glucose out of the liposome was the rate-determining step as compared to the relatively rapid skin permeation of the free solute. For the hydrophobic progesterone and hydrocortisone, quantitative analyses suggested direct transfer of drug from the liposome to the surface phases of skin and subsequent diffusion through the tissue. Considering this mechanism and owing to increased solubility of lipophilic drugs in liposomes, more total drug may be delivered through the skin by liposomes relative to simple aqueous solution.