ポストインサーション法によって調製したPEG修飾リポソームの表面物性に関する研究

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Post-insertion method is now widely used to modify liposomes with poly(ethylene glycol) (PEG) lipids. In this study, we examined the physicochemical properties of surface layers of distearoylphosphatidylethanolamine- PEG2000-modified liposomes composed of distearoylphosphatidylcoline, distearoylphosphatidylglycerol and cholesterol prepared in post-insertion method. Zeta potential measurements showed that the estimated aqueous layer thickness of PEG liposomes increases with increasing concentrations of PEG lipids added. Size exclusion chromatography demonstrated that the incorporation efficiency of PEG lipids into liposomes gradually decreases with increasing addition amount of PEG lipids. Quenching experiments of fluorescence-labeled PEG lipids confirmed that almost all PEG lipids distribute at the outermost layer of liposomes in the post-insertion preparation whereas PEG lipids distribute equally at inner and outer layers of liposomes in the conventional pre-mixed method. By correcting the incorporation efficiency and the outermost distribution of PEG lipids in liposomes, we found that the dependency of increases in aqueous layer thickness of PEG liposomes upon the outermost content of PEG lipids is similar in the both post-insertion and pre-mixed methods. Fluorescence resonance energy transfer measurements suggested that the increasing behavior of aqueous layer thickness is closely correlated with the conformational transition of PEG chains at the liposome surface. These results provide comparative information of the surface properties of PEG-modified liposomes prepared by the post-insertion and pre-mixed methods.

ポストインサーション法によって調製したPEG修飾リポソームの表面物性に関する研究

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