INFLUENCE OF SURFACE HYDROPHILICITY OF LIPOSOMES ON THEIR INTERACTION WITH PLASMA-PROTEIN AND CLEARANCE FROM THE CIRCULATION - STUDIES WITH POLY(ETHYLENE GLYCOL)-COATED VESICLES
INFLUENCE OF SURFACE HYDROPHILICITY OF LIPOSOMES ON THEIR INTERACTION WITH PLASMA-PROTEIN AND CLEARANCE FROM THE CIRCULATION - STUDIES WITH POLY(ETHYLENE GLYCOL)-COATED VESICLES
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DOI：
10.1016/0005-2736(91)90337-8
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发表时间：
1991-02-11
期刊：
影响因子：
--
通讯作者：
GREGORIADIS, G
中科院分区：
文献类型：
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作者：
SENIOR, J;DELGADO, C;GREGORIADIS, G
定义明确的脂质体系统先前已经建立了大小、表面电荷脂质组成和表面配体对脂质体中截留的模型化合物的体内命运和行为的影响。 在本研究中，定量保留水性标记物的脂质体通过二棕榈酰磷脂酰乙醇胺共价偶联到亲水性聚合物单甲氧基聚乙二醇（MPEG 5000）。 这种脂质体在血浆存在下保留涂层，并且似乎比没有聚合物的脂质体更慢地吸附血浆组分，使用含水两相分配技术显示。 在静脉内给药至小鼠后，MPEG偶联的脂质体从血液循环中的清除比没有MPEG的脂质体慢多达30%，尽管未修饰的脂质体具有先前显示的有利于实现最大半衰期的组成和尺寸。 有人建议，聚合物作为一个表面屏障，否则结合到血液中的脂质体和加速囊泡去除血浆因子。
Well-defined liposome systems have previously established the influence of size, surface charge lipid composition and surface ligands, on in vivo fate and behaviour of model compounds entrapped in lipisomes. In the present study, performed liposomes which quantitatively retain aqueous markers were covalenty coupled via dipalmitoylphophatidyl-ethanolamine, to the hydrophilic polymer, monomethoxypoly(ethylene glycol) (MPEG 5000). Such liposomes retain the coating in the presence of plasma, and appear to adsorb plasma components more slowly than liposomes without the polymer, shown using an aqueous two-phase partitioning technique. MPEG-coupled liposomes were cleared from the blood circulation up to 30% more slowly than liposomes without MPEG after intravenous administration to mice, despite the unmodified liposomes being of a composition and size shown previously to favour achievement of maximum half-life. It is suggested that the polymer acts as a surface barrier to plasma factors which otherwise bind to liposomes in the blood and accelerate vesicle removal.