Surface Pressure Analysis of Poly(ethylene oxide)-Modified Fusogenic Liposomes Incorporated into a Phospholipid Monolayer

Abstract

Fusogenic liposomes have a wide-range of applications as DDS and gene/protein delivery into living cells. A variety of surface modifications of drug carriers, to enable fusion with cells, have been proposed, however, the mechanism of fusion has still not been determined. To further improve the efficiency of drug carriers, a simple and easily examinable model of a living cell surface is needed. In this study, the time-course of a fusion phenomena was made by measuring the surface pressure increase of a phospholipid monolayer spread at the air/water interface due to the fusion of liposomes carrying PEO-lipid (dialkyl-terminated polyethylene oxide) reconstituted on their outer surface. The kinetics of the surface pressure change appeared to be bimodal, indicating the coexistence of different fusion pathways. It was found that the presence of the PEO-lipid on the liposome surface led to a faster lipid transfer compared to non-modified DMPC liposomes. This indicated that the reconstitution of PEO-lipid provided an alternative transfer pathway to that for non-fusogenic liposomes that show only a slow lipid transfer to phospholipid monolayers. The relation between the rate of fusion and the surface pressure of the host membrane is discussed.