Mechanical and interactive properties of lipid membranes containing surface-bound polymer
The rapid clearance, from the blood stream, of liposomes used in delivery systems is one of the major obstacles to advancing many applications of liposomes in medical technologies. The incorporation of glycolipids or a lipid that contains a large polymeric polar headgroup into the liposomes greatly enhances the circulation time of the injected dose in the blood. As a first step in understanding the physical mechanisms(s) operating in these processes, we have carried out a characterization of the mechanical and interactive properties of lipid bilayer systems of typical liposome formulations containing phospholipids, cholesterol, GMl and a polyethylene oxide lipid (PEOL). (Liposome Technology, Inc.). A micropipet manipulation method was used to determine the elastic area expansion modulus K, and several failure parameters of individual lipid vesicles. The repulsive, mutual interaction between lipid bilayers was examined by an x-ray method that measured the interbilayer gap separation as a function of applied pressure and also gave an indication of polymer-polymer interactions in the gap from electron density profiles. Compared to the hydrated lipid membrane, the inclusion of GMl and PEOL greatly increased the interbilayer separation distance, with the polymer producing the largest effect. In a low pressure regime, the exponential decay constant was -8 to 10 A for both surface groups, before a stiffer repulsive interaction appeared at high pressure and close separation. Even though the precise mechanism of action is not yet known, it is clear that the presence of surface bound moieties act to increase repulsive interactions and may also inhibit opsonization of the liposomes, thereby evading identification to the RES.
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