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聚天冬氨酸及其衍生物是一种具有良好生物相容性和可生物降解性的高分子材料,被广泛应用于生物医药领域.本研究通过大分子引发剂ω-胺基-α-甲氧基聚乙二醇引发N-羧基-α-氨基环内酸酐开环聚合和N-(3-氨丙基)咪唑侧基改性,制备了一种侧链含有咪唑丙基的聚乙二醇-聚(咪唑丙基-天冬酰胺)-聚丙氨酸三嵌段共聚物.在水溶液中,此聚合物可自组装形成一种核-壳-冠型的三层共聚物胶束,其中疏水性的聚丙氨酸链段自聚集形成胶束的核,聚(咪唑丙基-天冬酰胺)链段形成具有pH-响应性的壳层,用于包埋和释放药物,外围的聚乙二醇链段可以提供一个稳定的水合冠层,延长药物的体内循环时间.利用咪唑环与游离阿霉素之间的π-π相互作用和疏水相互作用可以在自组装的过程中将阿霉素包埋到胶束内.研究发现,载药胶束随环境pH值的降低药物的释放速率显著增加.这主要是由于咪唑环在酸性条件下的质子化导致链段亲疏水性质发生明显变化.
Polyaspartic acid and its derivatives are a kind of polymer materials with good biocompatibility and biodegradability and are widely used in the field of biomedicine.In this study, macromolecular initiator ω-amino-α- Methoxypolyethylene glycol initiates ring-opening polymerization of N-carboxy-α-aminocyclic anhydride and modification of pendant N- (3-aminopropyl) imidazole to prepare a polyethylenimine Poly (imidazolylpropyl-asparagine) -polylalanine triblock copolymer.In aqueous solution, the polymer can self-assemble to form a core-shell-crown type three-layer copolymer micelles, Wherein the hydrophobic polyalanine segments self-assemble to form micellar nuclei, the poly (imidazolyl-asparagine) segments form a pH-responsive shell for embedding and releasing the drug, the peripheral poly Ethylene glycol segments can provide a stable hydrated canopy that extends the drug’s in vivo circulation time.Using the π-π interaction and hydrophobic interaction between the imidazole ring and the free doxorubicin, Inoculated with micelles, the study found that the release rate of drug-loaded micelles significantly increased with decreasing pH of the environment. Since the imidazole ring protons under acidic conditions results in the segment Hydropathy properties change significantly.