聚(2-乙基丙烯酸)脂肪酰胺衍生物构建的酸敏脂质体

本实验合成了系列聚(2-乙基丙烯酸)长链脂肪酰胺衍生物，并采用高分子插入法制备了聚(2-乙基丙烯酸)酸敏高分子脂质体。应用荧光指示剂、粒径仪、荧光显微镜及细胞实验，系统研究了高分子修饰和脂肪胺的链长对高分子衍生物嵌入脂质体的效率和质量的影响。结果表明，高分子插入法可以制备聚(2-乙基丙烯酸)酸敏高分子脂质体。(1) 高分子嵌入量与高分子脂肪胺的链长无关，但与高分子修饰度相关。(2) 高分子嵌入量与起始的高分子-脂质体比例成正比。(3) 在酸性条件下聚(2-乙基丙烯酸)脂质体可产生显著的脂质体融合及释药行为。(4) 聚(2-乙基丙烯酸)脂质体在细胞内呈现出良好的酸敏诱导释药特性。实验证明这种方法制备的脂质体具有良好的酸敏释药性能，并且制备方法简便，可控性好，实用性强。

Acid-sensitive polymer liposomes prepared by poly(2-ethylacrylic acid) alkylamide derivatives

Poly(2-ethylacrylic acid)(PEAA) alkylamide derivatives were synthesized for constructing pH-sensitive liposomes by partially modification of carboxylic groups of PEAA with chemical reaction.These lipid derivatives of PEAA were synthesized by partially modification of carboxylic groups of PEAA with alkylamines.The acid-sensitive polymer associated liposomes were obtained by the method of polymer self-insertion in aqueous solutions through inserting hydrophobic lipid anchors of the polymer PEAA derivatives into the outer layer of vesicles.Factor effects on polymer insertion into liposomes were evaluated and the pH-sensitivity of the polymer associated liposomes was studied by calcein release assay.The PEAA-associated-liposomes were prepared successfully by the methods of self-insertion.The PEAA-associated-liposomes are shown to be stable at neutral pH.(1) There was no correlate of anchor density of PEAA with length of the alkyl chain,but was positively correlated with the degree of PEAA modification.(2) Polymer insertion increased with initial ratio of polymer to lipid.(3) Under acidic conditions the associated polymer induces membrane disruption and fusion.(4) The PEAA-associated-liposomes shown pH-sensitive drug release property under acidic conditions.The anchored-poly(ethylacrylic acid) lipid derivatives can be useful in developing a potential pH sensitive drug delivery system.