INTERACTIONS BETWEEN LIPOSOMES AND HUMAN STRATUM-CORNEUM STUDIED BY FREEZE-SUBSTITUTION ELECTRON-MICROSCOPY

Vesicular systems such as liposomes have been applied for the percutan eous delivery of drugs. Successful percutaneous delivery relies strong ly on an adequate reduction of the barrier properties of the stratum c orneum, which is considered to constitute the main barrier of the skin . In this study, the mechanisms by which liposomes interact with the h uman stratum corneum were investigated using freeze-substitution elect ron microscopy in combination with ruthenium tetroxide fixation. A liq uid-state liposome suspension, containing dilaurylphosphatidylcholine (DLPC) was compared with two gel-state liposome suspensions, containin g distearylphosphatidylcholine (DSPC) and ceramides. In addition, the influence of cholesterol sulphate, a component of the skin lipids, was studied. Comparing the liquid-state with the gel-state liposomes, we observed that both gel-state liposome suspensions were able to form la rge stacks and networks of lipid bilayers at the surface of the stratu m corneum in contrast to the liquid-state DLPC liposomes, which showed no adsorption. Deeper down in the stratum corneum inter- and intracel lular interactions were observed for the DLPC liposomes, whereas inter cellular interactions were observed only for the gel-state liposomes t o which cholesterol sulphate was added. Incorporation of cholesterol s ulphate in the DLPC-liposomes had no influence on their mechanism of i nteraction. (C) 1998 Elsevier Science B.V. All rights reserved.