Influence of liposomal drug entrapment on percutaneous absorption

Abstract

Results of permeation experiments involving finite dose diffusion cells with hairless mouse skin as the membrane indicate that neither intact liposomes nor the phospholipid of which they are comprised diffuses across the skin. Lipophilic drugs like progesterone and hydrocortisone, which are intercalated within the bilayer structure of the phospholipid in multilamellar liposomes, seem to pass through the skin with comparable facility to free drug (comparable mass transfer coeficients). On the other hand, highly polar glucose entrapped in the aqueous compartments of the liposome is poorly available for transport. The results of in vitro release rate studies and theoretical calculations indicate that the very slight flux of liposomally incorporated glucose seen experimentally is attributable to a slow release rate of glucose out of the liposome followed by relatively rapid skin permeation of the free solute. On the other hand, for hydrophobic progesterone and hydrocortsone the experimental results and supportive theoretical analysis suggest direct transfer of drug from liposome to the skin. Considering this mechanism and owing to increased soluble payloads of lipophilic drugs through liposomal incorporation, n ore total drug may be delivered through skin via liposomes relative to simple aqueous solutions.