酸敏高分子诱导的脂质体膜融合性能研究  

Property of liposomal fusion induced by acid-sensitive polymer

作　　者：王汝涛[1] 陈涛[1] 王昭 惠民权[1] 傅经国[2] 

机构地区：[1]西北工业大学生命科学院,陕西西安710072 [2]陕西省脂质体工程技术研究中心,陕西西安710075

出　　处：《药学学报》2008年第9期951-955,共5页Acta Pharmaceutica Sinica

基　　金：陕西省重大科技创新项目(2006ZKC04)

摘　　要：本文研究了具有酸敏特性的高分子聚(2-乙基丙烯酸)诱导的脂质体-脂质体及脂质体-细胞膜之间的融合特性。采用脂肪胺修饰的聚(2-乙基丙烯酸)制备酸敏高分子脂质体。用荧光共振能量转移法定量测定脂质体间的融合程度,采用粒径仪研究脂质体在发生膜融合时的粒径变化。结果显示,聚(2-乙基丙烯酸)酸敏高分子脂质体有很强的酸敏融合性能。在酸性条件下高分子酸敏脂质体之间可以相互融合,其程度与脂质体表面酸敏高分子聚(2-乙基丙烯酸)的分子质量成正比;高分子酸敏脂质体的酸敏融合性与构成其磷脂膜的磷脂种类有关,另外脂质体膜中加入胆固醇可降低高分子酸敏脂质体的膜融合性能;高分子酸敏脂质体与血红细胞膜影融合;酸敏高分子诱导的脂质体融合会引起脂质体膜通透性的增加。聚(2-乙基丙烯酸)诱导的酸敏高分子脂质体的膜融合特性说明其可用于制备酸敏控释脂质体。The fusion between liposome-liposome, liposome-biomembarnes induced by acid-sensitive polymers has been systematically investigated. The polymer-liposomes were constructed by post-insertion method with the poly （2-ethylacrylic acid ） （PEAA） alkylamide derivatives. The liposomal fusion was studied by use of fluorescence resonance energy transfer assay, particle size, fluorescent-photometer. The results indicated that the poly （2-ethylacrylic acid ）-liposomes has very strong acidic induced fusion capability. Under acidic conditions, acid-sensitive polymer liposomes fused each other, the fusion closely related to the molecular weight of acid sensitivity polymer on the surface of liposomes. The acidic fusion of polymer-liposomes was dependent upon the lipids composition, the degree of fusion was reversely related to the cholesterol contents. Acid-sensitive polymer liposomes fused with erythrocyte ghosts. The liposomal fusion induced by acid-sensitive polymer associated with the increase of membrane permeability. The good acid-sensitivity of PEAA has been further demonstrated by membrane fusion in current experiments, and the liposomes prepared with lipid anchored-poly （2-ethylacrylic acid ） were developed as a potential pH sensitive delivery system.

关 键 词：酸敏高分子脂质体 聚(2-乙基丙烯酸) 膜融合 荧光共振能量转移法 

分 类 号：R943.4[医药卫生—药剂学]