NEW STERICALLY STABILIZED VESICLES BASED ON NONIONIC SURFACTANT, CHOLESTEROL, AND POLY(ETHYLENE GLYCOL)-CHOLESTEROL CONJUGATES

Monomethoxypoly(ethylene glycol) cholesteryl carbonates (M-PEG-Chol) w ith polymer chain molecular weights of 1000 (M-PEG1000-Chol) and 2000 (M-PEG2000-Chol) have been newly synthesized and characterized. Their aggregation behavior in mixture with diglycerol hexadecyl ether (C(16) G(2)) and cholesterol has been examined by cryotransmission electron m icroscopy, high-performance gel exclusion chromatography, and quasiela stic light scattering. Nonaggregated, stable, unilamellar vesicles wer e obtained at low polymer levels with optimal shape and size homogenei ty at cholesteryl conjugate/ lipids ratios of 10 mol% M-PEG1000-Chol o r 5 mol% M-PEG2000-Chol, corresponding to the theoretically predicted brush conformational state of the PEG chains. At 20 mol% M-PEG1000-Cho l or 10 mol% M-PEG2000-Chol, the saturation threshold of the C(16)G(2) /cholesterol membrane in polymer is exceeded, and open disk-shaped agg regates are seen in coexistence with closed vesicles. Higher levels up to 30 mol% lead to the complete solubilization of the vesicles into d isk-like structures of decreasing size with increasing PEG content. Th is study underlines the bivalent role of M-PEG-Chol derivatives: while behaving as solubilizing surfactants, they provide an efficient steri c barrier, preventing the vesicles from aggregation and fusion over a period of at least 2 weeks.