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目的:合成双嵌段共聚物材料聚(2-乙基-2-噁唑啉)-聚乳酸(PEOz-PLA),制备紫杉醇pH敏感嵌段共聚物胶束,并对其体外性质进行评价。方法:用~1HNMR和红外光谱对聚合物结构进行表征,采用透析法制备紫杉醇载药胶束,对冻干胶束的冻干保护剂种类进行筛选,芘荧光探针法测定胶束的临界胶束浓度(CMC),动态光散射法(DLS)对胶束的粒径分布进行测定,透析法测定载药胶束在不同pH条件下的体外释药行为。结果:胶束的临界胶束浓度为25.63 mg·ml~(-1),以10%聚乙二醇4000作为冻干保护剂胶束复溶性好,粒径分布窄,胶束载药量为8.12%,包封率为69.33%,冻干胶束平均粒径为183.7 nm;在pH 7.4释放介质中,胶束释药缓慢,而在pH 5.0条件下,胶束释药速率明显加快,体现出胶束释药行为的pH敏感性。结论:PEOz-PLA聚合物胶束制备工艺简单,其粒径、包封率和载药量可控,具有一定的缓释作用,为其进一步的药理与临床应用提供依据。
OBJECTIVE: To synthesize poly (2-ethyl-2-oxazoline) -polylactic acid (PEOz-PLA) as diblock copolymer and prepare paclitaxel pH-sensitive block copolymer micelles and to evaluate its in vitro properties. METHODS: The structure of the polymer was characterized by ~ 1HNMR and IR spectroscopy. The paclitaxel drug-loaded micelles were prepared by dialysis method. The lyophilized micelles were screened by pyrene fluorescence probe method. The critical micelles (CMC) and dynamic light scattering (DLS) were used to determine the particle size distribution of micelles. The in vitro drug release behavior of drug-loaded micelles at different pHs was determined by dialysis method. Results: The micelles had a critical micelle concentration of 25.63 mg · ml -1. With 10% PEG 4000 as a lyoprotectant, the micelles showed good re-solubility and a narrow particle size distribution with a micellar drug loading of 8.12%, the entrapment efficiency was 69.33%, the average diameter of lyophilized micelles was 183.7 nm. The release of micelles was slow at pH 7.4, while the release rate of micelles was significantly increased at pH 5.0. PH sensitivity of drug release behavior of micelles. Conclusion: The preparation process of PEOz-PLA polymer micelles is simple, and its particle size, entrapment efficiency and drug loading can be controlled, and has a certain sustained release effect, providing the basis for further pharmacological and clinical applications.