pH敏感聚合物胶束的制备及体外抗肿瘤活性研究  

Preparation and in vitro antitumor activity of pH-sensitive polymer micelles

作　　者：单晓甜 毛静 邱立朋 陈敬华 SHAN Xiao-tian;MAO Jing;QIU Li-peng;CHEN Jing-hua(School of Pharmaceutical Sciences,Jiangnan University,Wuxi 214122,China)

机构地区：[1]江南大学药学院,无锡214122

出　　处：《中国新药杂志》2020年第7期810-815,共6页Chinese Journal of New Drugs

基　　金：国家自然科学基金资助项目(81503007,21574059)。

摘　　要：目的:本研究合成原酸酯作为连接体,合成pH敏感两亲性聚合物单甲氧基聚乙二醇-原酸酯-十八烷(mPEG-OE-C18),制备载阿霉素的聚合物胶束(DOX/mPEG-OE-C18),并考察体外抗肿瘤活性。方法:采用化学偶联合成mPEG-OE-C18,通过超声法制备载阿霉素的聚合物胶束,并对胶束的粒径、包封率和体外药物释放等性质进行考察,同时采用人胃癌MGC80-3细胞进行体外细胞细胞毒性评价。结果:制备的DOX/mPEG-OE-C18胶束呈类球形,粒径为(182.6±5.1) nm,电位为(0.122±0.04) mV,载药胶束的包封率高达(97.17±2.74)%。DOX/mPEG-OE-C18胶束在pH 5.0下的释放快于pH 7.4,具有明显的pH敏感性。体外细胞毒性实验表明,空白载体对细胞毒性较小,且载药胶束对MGC80-3细胞具有较好的杀伤作用。结论:DOX/mPEG-OE-C18胶束具有明显的pH敏感性和抗肿瘤效果,有望将其应用为抗肿瘤药物载体。Objective: Orthoesters were used to synthesize the construction of pH-sensitive amphiphilic polyethylene glycol-orthoester-octadecane(mPEG-OE-C18) polymers, and then doxorubicin-loaded polymer micelles(DOX/mPEG-OE-C18) were prepared, and the in vitro antitumor activity was investigated. Methods: mPEG-OE-C18 polymers were synthesized by chemical coupling method. The polymer micelles were prepared by ultrasonic method, and the particle size, encapsulation efficiency and in vitro drug release of the micelles were investigated. Furthermore, in vitro cell cytotoxicity against human gastric cancer MGC80-3 cells was evaluated. Results:The prepared DOX/mPEG-OE-C18 micelles were spherical structure. And the particle size and zeta potential were(182.6±5.1) nm and(0.122±0.04) mV, respectively. The encapsulation efficiency of drug-loaded micelles was(97.17±2.74)%. The drug released from DOX/mPEG-OE-C18 micelles at pH 5.0 was faster than that at pH 7.4, indicating the micelles is significantly pH-sensitive. In vitro cytotoxicity experiments showed that the blank micelles were nontoxic, while the drug-loaded micelles presented enhanced antitumor effect on MGC80-3 cells. Conclusion: DOX/mPEG-OE-C18 micelles with obvious pH sensitivity and antitumor effect are expected to be used as carriers of antitumor drug.

关 键 词：阿霉素 聚乙二醇 PH敏感 聚合物胶束 

分 类 号：R914[医药卫生—药物化学] R96[医药卫生—药学]