PEGylation of microspheres generates a heterogeneous population of particles with differential surface characteristics and biological performance
PEGylation of microspheres generates a heterogeneous population of particles with differential surface characteristics and biological performance
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DOI：
10.1016/s0014-5793(02)03710-9
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发表时间：
2002-12-18
期刊：
影响因子：
3.5
通讯作者：
Moghimi, SM
中科院分区：
文献类型：
--
作者：
Gbadamosi, JK;Hunter, AC;Moghimi, SM
用甲氧基聚乙二醇-5000 （mPEG-5000）对聚苯乙烯微球进行表面聚乙二醇修饰，产生了不同表面特征和体外生物性能（吞噬和补体活化）的异质实体群体。表面非均质性是通过疏水相互作用色谱法、粒子电泳迁移率测量和投影mPEG链的层厚来确定的。疏水相互作用层析对J774 A1类巨噬细胞的吞噬作用与粒子zeta电位呈显著的线性关系。以高密度蘑菇刷状中间和/或刷状结构为主的mPEG分子表面的微球群体对吞噬的抵抗力最强，对人体补体系统的激活能力较差。相反，那些在蘑菇状态下具有显性表面mpeg的群体是补体系统的有效激活剂，并且易于吞噬。因此，表面异质性解释了为什么静脉注射的“长循环”纳米颗粒的一部分被网状内皮系统的巨噬细胞迅速清除。疏水相互作用色谱可以很容易地评估聚乙二醇化颗粒药物递送系统的表面异质性程度，并预先选择具有最佳血液保留时间的颗粒。这些观察结果也可能与细胞、药物仓库和植入式装置的成功表面伪装有关。(C) 2002年欧洲生化学会联合会。Elsevier Science B.V.版权所有。
Surface PEGylation of polystyrene microspheres with methoxy-poly(ethylene glycol)-5000 (mPEG-5000) generated a heterogeneous population of entities that differed in surface characteristics and in vitro biological performance (phagocytosis and complement activation). Surface heterogeneity was determined by hydrophobic interaction chromatography, measurements of particle electrophoretic mobility in a defined field and adlayer thickness of the projected mPEG chains. The particle population separation by hydrophobic interaction chromatography demonstrated a remarkable linear relationship between the particle zeta potential and phagocytosis by J774 A1 macrophage-like cells. Microsphere populations bearing a predominant surface of mPEG molecules as high-density mushroom-brush intermediate and/or brush configuration were most resistant to phagocytosis and activated the human complement system poorly. Conversely, those populations with predominant surface mPEGs in a mushroom regime were potent activators of the complement system and were prone to phagocytosis. Therefore, surface heterogeneity explains why a fraction of intravenously injected 'long-circulating' nanoparticles is cleared rapidly by macrophages of the reticuloendothelial system. Hydrophobic interaction chromatography can readily assess the extent of surface heterogeneity of PEGylated particulate drug delivery systems and pre-select particles with optimal retention times in the blood. These observations may also be relevant with respect to successful surface camouflaging of cells, drug depots and implantable devices. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.