INTERACTION OF LIPOSOMES WITH HUMAN SKIN IN-VITRO - THE INFLUENCE OF LIPID-COMPOSITION AND STRUCTURE

Liposomes have been suggested as a vehicle for dermal and transdermal drug delivery, but the knowledge about the interaction between lipid v esicles and human skin is poor. Therefore, we visualized liposome pene tration into the human skin by confocal laser scanning microscopy (CLS M) in vitro. Liposomes were prepared from phospholipids in different c ompositions and labeled with a fluorescent lipid bilayer marker, N-Rh- PE (L-alpha-phosphatidylethanolamine-N-lissamine rhodamine B sulfonyl) . Fluorescently labelled liposomes were not able to penetrate into the granular layers of epidermis. However, the fluorescence from liposome compositions containing DOPE (dioleylphosphatidyl ethanolamine) was a ble to penetrate deeper into the stratum corneum than that from liposo mes without DOPE. Pretreatment of skin with unlabeled liposomes contai ning DOPE or lyso-phosphatidyl choline (lyso-PC) enhanced the subseque nt penetration of the fluorescent markers, N-Rh-PE and sulforhodamine B into the skin, suggesting possible enhancer activity, while most lip osomes did not show such enhancement. Resonance energy transfer (RET) and calcein release assay between stratum corneum lipid liposomes (SCL Ls) and the phospholipid vesicles suggested that the liposomes contain ing DOPE may fuse or mix with skin lipids in vitro and loosen the SCLL bilayers, respectively. Among the factors not affecting stratum corne um penetration were: negative charge, cholesterol inclusion and acyl c hain length of the phospholipids. In conclusion, fusogenicity of the l iposome composition appears to be a prerequisite for the skin penetrat ion.