中文摘要：

本文采用透析法制备了新型温度/pH双敏感聚组氨酸-聚乳酸羟基乙酸-聚乙二醇-聚乳酸羟基乙酸-聚组氨酸（PHis-b-PLGA-b-PEG-b-PLGA-b-PHis）嵌段共聚物的空白胶束与阿霉素（DOX）载药胶束。采用荧光探针技术测定其临界胶束浓度（CMC）;应用光透射法研究了聚合物胶束的温度和pH敏感性质;测定了阿霉素载药胶束的粒径、形态、包封率和载药量;并对阿霉素载药胶束的温度和pH响应释药行为进行了研究。结果表明,制备的嵌段共聚物的临界胶束浓度为7.5×10-3 g.L-1;随胶束溶液温度升高或pH降低,其透光率升高;载药胶束的包封率为（85.2±3.1）%,载药量为（10.4±4.5）%;载药胶束粒径为（91.1±15.8）nm,为类球形结构;与模拟生理条件下（37℃,pH 7.4）释药行为相比,升高温度（41℃）、降低pH（pH 7.0、pH 6.5、pH 5.0）和同时升温并降低pH（41℃,pH 5.0）后胶束释药行为明显加快,表明该胶束的释药行为具有温度和pH敏感性。研究结果可见,PHis-b-PLGA-b-PEG-b-PLGA-b-PHis共聚物胶束具有pH/温度双重响应性质,有望成为抗肿瘤药物的智能型控释载体。

英文摘要：

The dialysis method was employed to prepare blank and doxorubicin（DOX） loaded micelles formed by temperature-and pH-sensitive polyhistidine-co-polyDL-lactide-co-glycolide-co-polyethyleneglycol-co-polyDL-lactide-co-glycolide-co-polyhistidine（PHis-b-PLGA-b-PEG-b-PLGA-b-PHis）.The critical micelle concentrations（CMC） of the copolymers were measured with Pyrene Fluorescent Probe Technique.The temperature-and pH-sensitive properties of the blank micelles solution were investigated by optical transmittance measurement.The morphology and diameter of DOX micelles were characterized by transmission electron microscopy（TEM） and dynamic light scattering（DLS）.The entrapment rate and drug-loading rate were determined with dialysis method.The in vitro release study was further performed to examine the temperature-and pH-responsive drug release behavior from DOX-loaded micelles.The results indicated that the CMC,entrapment efficiency and drug-loaded amount of the micelles were 7.5 × 10-3 g·L-1,85.2 ± 3.1% and 10.4 ± 4.5%,respectively.The DOX micelle was globular-shaped with a mean diameter of 91.1 ± 15.8 nm.The transmittance of micelle solution consistently increased with the increasing temperature or decreasing pH.In comparison to the drug release profile at physiological conditions（37 ℃,pH 7.4）,the DOX-loaded micelles showed faster drug release rate at higher temperature（41 ℃）,lower pH（pH 7.0,pH 6.5,pH 5.0） or higher temperature and lower pH（41 ℃,pH 5.0）.This indicated that the micelles showed a temperature and pH-triggered drug release pattern.Base on the above results,it can be concluded that PHis-b-PLGA-b-PEG-b-PLGA-b-PHis block copolymer micelles which respond to temperature and pH stimuli are promising smart carriers for anti-tumor drugs with the advantages of temperature-and pH-triggered drug release.