还原、温度和pH三重响应性交联聚合物载药胶束的制备及其释药性能研究  

The preparation and study on drug release of a triply-responsive(redox/thermo/pH)cross-linked polymeric micelle as anti-cancer drug carrier

作　　者：屈婧 陈康隆 王秋月[1] 林娟[2] 周庆翰[1] 

机构地区：[1]西南民族大学化学与环境保护工程学院,成都610041 [2]成都医学院生物医学系,成都610083

出　　处：《生物医学工程学杂志》2018年第1期70-80,共11页Journal of Biomedical Engineering

基　　金：国家自然科学基金青年科学基金项目(21404086);四川省科技厅应用基础研究项目(18YYJC0265);四川省教育厅资助项目(16ZA0284);西南民族大学研究生创新型科研项目(CX2018SZ130)

摘　　要：本文利用自由基共聚法合成了一种多重响应性交联聚合物载药胶束,对其化学结构、纳米级形貌进行了表征,并测定其载药率。实验结果表明,交联聚合物载药胶束为尺寸约100 nm的球形颗粒;其在还原剂谷胱甘肽(GSH)作用下可发生降解并溶胀;交联聚合物载药胶束的低临界溶液温度(LCST)为39.4℃,当环境温度高于LCST时,该胶束结构发生明显收缩。本研究分析了该交联聚合物载药胶束在模拟肿瘤微环境下的载药释放情况,即当该交联聚合物载药胶束处于酸性(p H 5.0)、还原性(GSH 10 mmol/L)和高温(42.0℃)条件下时,受条件刺激可促进其中药物释放,其累积释放率可达91.78%,而该交联聚合物载药胶束在无刺激条件下累积释放率仅为1.12%。细胞毒性实验进一步表明,本文合成的交联聚合物载药胶束表现出了较强的细胞摄取能力,具有良好的生物相容性和较好的体外抗肿瘤活性。基于以上研究结果,本实验中制备的交联聚合物载药胶束具有多重响应性释药功能,有望成为一种具备高效可控释药功能的理想载体材料。A multiple-stimuli-responsive drug-conjugated cross-linked micelles was prepared by radical copolymerization. The chemical structure, morphology, and size of the cross-linked micelles were characterized, and the drug loading of the micelle was calculated. The experimental results indicated that the hydrodynamic size of the drugloaded micelles were about 100 nm, and the as prepared micelles could be degraded and swelled in presence of reducing glutathione （GSH）. The low critical solution temperature （LCST） of the rnicelle was around 39.4℃. According to the experimental results, the micelles will shrink at temperature above the LCST. Subsequently, the accumulative drug release rate was up to 91.78% under acidic （pH 5.0）, reductive （GSH 10 mmol/L） and high temperature （42.0℃） conditions mimicking the tumor microenvironment, while a relatively low release rate of 1.12% was observed without stimulation. The drug-conjugated cross-linked micelles showed a strong cell uptake behavior. In the cytotoxicity assay, the micelles exhibited effective anti-cancer activity and excellent biocompatibility. In brief, the experimental results show that the as- prepared drug-conjugated cross-linked micelle exhibits multiple stimuli-responsiveness, which holds great promise for anti-cancer drug delivery.

关 键 词：交联聚合物载药胶束 还原响应性 PH敏感性 温度敏感性 药物释放 

分 类 号：R943[医药卫生—药剂学]