Bilayer stability and impermeability of nonionic surfactant vesicles sterically stabilized by PEG-cholesterol conjugates

New vesicles based on diglycerol hexadecyl ether (C(16)G(2)), cholesterol and monomethoxypoly(ethylene glycol) cholesteryl carbonate (M-PEG-Chol) were prepared by ultrasonic irradiation and characterized regarding their size stability and membrane impermeability. The influence of polymer level and hydrophilic chain length (1000 or 2000 molecular weight) was studied and the performances compared to those of conventional nonionic surfactant vesicles (NSV) composed of C(16)G(2), cholesterol and dicetylphosphate. Intrinsic physical stability at 20 degrees C was evaluated by following versus time both the evolution of vesicle mean diameter (MD) by quasi-elastic light scattering and the release of encapsulated calcein by high performance gel exclusion chromatography coupled with fluorescence and 90 degrees light scattering on-line detections. Good size stability and calcein retention ability (less than 15% leakage), comparable to NSV, were observed over a fortnight. Longer incubation times yielded slight increase in size; 25-40% leakages were found, against 17% for NSV. Membrane impermeability was also assessed through the resistance to octyl glucoside. M-PEG-Chol-containing vesicles presented slow solubilization kinetics mainly governed by surface density of hydrophilic chains. The most efficient steric barrier was achieved at 10 mol% M-PEG1000-Chol (5 mol% M-PEG2000-Chol), which corresponds to the brush conformational slate of the chains. (C) 1998 Academic Press.