Bedu-Addo F K, Tang P, Xu Y, Huang L
The Liposome Company, Princeton, New Jersey 08540, USA.
Pharm Res. 1996 May;13(5):718-24. doi: 10.1023/a:1016043431778.
The purpose of this study was to investigate polyethyleneglycol (PEG)-phosphatidylethanolamine (PE) conjugate interaction with cholesterol-phospholipid mixtures in an attempt to explain the effect of cholesterol on liposome circulation time.
Differential scanning calorimetry, NMR, electron microscopy, dynamic light scattering and fluorescence spectroscopy were the major methods used.
Studies performed in the absence of cholesterol indicated the formation of three distinct physical states depending on the chain length of PEG in PEG-PE. Mixed micelle formation was observed at concentrations of PEG(1,000)-DPPE above 7 mol-% of lipid. Phase separated lamellae were observed at all concentrations of PEG( 12,000)-DPPE (Bedu-Addo et al. Pharm. Res. 13:710-717 (1996)). Upon incorporation of high concentrations of cholesterol >30 mol% into the lipid bilayer, the formation of phase separated lamellae was completely inhibited and the formation of mixed micelles significantly reduced. At high concentrations of PEG(1,000)-PE, solubilization of the bilayer occurred with preferential solubilization of cholesterol over phosphatidylcholine. Maximum steric stabilization (surface protection) was observed with low concentrations of short chain PEG-PE and high concentrations of cholesterol.
The study provides a physical mechanism for the following observations: the blood circulation time is significantly increased or decreased with liposomes highly enriched with cholesterol or PEG-PE respectively.
本研究旨在探究聚乙二醇（PEG）-磷脂酰乙醇胺（PE）共轭物与胆固醇-磷脂混合物的相互作用，以解释胆固醇对脂质体循环时间的影响。
主要使用差示扫描量热法、核磁共振、电子显微镜、动态光散射和荧光光谱法。
在无胆固醇条件下进行的研究表明，根据PEG-PE中PEG的链长会形成三种不同的物理状态。当PEG(1,000)-DPPE浓度高于脂质的7 mol-%时，观察到混合胶束的形成。在所有PEG(12,000)-DPPE浓度下均观察到相分离的片层（贝杜-阿多等人，《药物研究》13:710 - 717(1996)）。当向脂质双层中加入高浓度（>30 mol%）的胆固醇时，相分离片层的形成被完全抑制，混合胶束的形成显著减少。在高浓度的PEG(1,000)-PE时，双层发生溶解，胆固醇比磷脂酰胆碱更易被优先溶解。在低浓度的短链PEG-PE和高浓度的胆固醇条件下观察到最大空间稳定作用（表面保护）。
该研究为以下观察结果提供了一种物理机制：分别富含胆固醇或PEG-PE的脂质体的血液循环时间会显著增加或减少。
