Moribe K, Maruyama K, Iwatsuru M
Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan.
Chem Pharm Bull (Tokyo). 1997 Oct;45(10):1683-7. doi: 10.1248/cpb.45.1683.
Poly(ethylene glycol)-coated liposomes (PEG-liposomes) were prepared from distearoylphosphatidylcholine (DSPC)/cholesterol (Ch) (1:1, molar ratio) with various amounts of distearoyl-N-(monomethoxy poly(ethylene glycol)succinyl)phosphatidylethanolamine (DSPE-PEG). Surface potentials of PEG-liposomes showed negative values, however, the zeta potentials were almost neutral under physiological conditions (150 mM NaCl). Taking these electrical surface properties into consideration, a non-charge-sensitive phase system consisting of 5% PEG8000 and 5% dextran T-500, 0.01 M sodium phosphate, 0.15 M sodium chloride (pH 7.0) was used to estimate the alteration of surface state of PEG-liposomes after interaction with plasma in vitro and in vivo. PEG-liposomes showed increased partitioning to the PEG phase with increasing amount of DSPE-PEG. One hundred percent partitioning to the PEG phase was obtained when 2 or 1 mol% of DSPE-PEG1K or 2K was incorporated into the liposomes, respectively. This PEG/lipid ratio (mol/mol) thus afforded complete protection of the liposomal surface by the PEG moiety. When these PEG-liposomes were incubated with plasma protein (in vitro) or were recovered from liposome-injected mice (in vivo), they showed decreased partitioning to the PEG phase. However, when the in vivo-treated PEG-liposomes were purified by column chromatography and ultracentrifugation, their partitioning to the PEG phase was restored to that of PEG-liposomes incubated in phosphate-buffered saline. Thus although PEG acts as a steric barrier against the attachment of plasma protein to the liposome surface and slows down liposome clearance from the circulation in vivo, a weak interaction remains between PEG-liposome and plasma protein when the incorporated amount of DSPE-PEG is low.
聚乙二醇包被的脂质体（PEG 脂质体）由二硬脂酰磷脂酰胆碱（DSPC）/胆固醇（Ch）（摩尔比 1:1）与不同量的二硬脂酰 -N -（单甲氧基聚乙二醇琥珀酰）磷脂酰乙醇胺（DSPE - PEG）制备而成。PEG 脂质体的表面电位显示为负值，然而，在生理条件（150 mM NaCl）下，其ζ电位几乎呈中性。考虑到这些表面电学性质，使用由 5% PEG8000、5% 葡聚糖 T - 500、0.01 M 磷酸钠、0.15 M 氯化钠（pH 7.0）组成的非电荷敏感相系统来评估 PEG 脂质体在体外和体内与血浆相互作用后表面状态的变化。随着 DSPE - PEG 量的增加，PEG 脂质体在 PEG 相中的分配增加。当分别将 2 或 1 mol% 的 DSPE - PEG1K 或 2K 掺入脂质体时，可实现 100% 分配到 PEG 相。因此，这种 PEG/脂质比（mol/mol）通过 PEG 部分为脂质体表面提供了完全保护。当这些 PEG 脂质体与血浆蛋白在体外孵育或从注射脂质体的小鼠体内回收时，它们在 PEG 相中的分配减少。然而，当对体内处理的 PEG 脂质体进行柱色谱和超速离心纯化后，它们在 PEG 相中的分配恢复到在磷酸盐缓冲盐水中孵育的 PEG 脂质体的水平。因此，尽管 PEG 作为空间屏障可防止血浆蛋白附着于脂质体表面并减缓脂质体在体内循环中的清除，但当 DSPE - PEG 的掺入量较低时，PEG 脂质体与血浆蛋白之间仍存在弱相互作用。
