pH响应型星状聚合物胶束的制备及释药性能

Synthesis of pH-Responsive Star-Shaped Polymeric Micelles for Controlled Drug Delivery

以金刚烷为核设计合成了一种具有pH响应功能的四臂星状聚合物金刚烷-[聚(乳酸-共-羟基乙酸)-聚甲基丙烯酸二乙氨基乙酯-聚(乙二醇)单甲醚]4(4sAd-PLGA-D-P),制备了4sAd-PLGA-D-P自组装胶束,考察了该胶束对抗癌药物阿霉素(Doxorubicin,DOX)的控释性能。结果表明:改变聚甲基丙烯酸二乙氨基乙酯(PDEAEMA)的链段长度可实现对聚合物胶束性能的调控。PDEAEMA链段越长,聚合物胶束的粒径越大,载药量越高,药物累计释放量越高。聚合物胶束具有良好的稳定性(临界胶束浓度(Critical Micelle Concentration,CMC)为0.0031 mg/mL)、pH响应性能和载药能力(载药量高达24.8%)。载DOX胶束在肿瘤微环境pH值(pH=5.0)的累计释放量(85.2%)明显高于正常组织pH=7.4条件下的累计释放量(20.9%),可实现抗癌药物的可控释放。因此,pH响应型聚合物胶束4sAd-PLGA-D-P在抗癌药物递送领域具有潜在的应用前景。

A four arm star-shaped pH responsive polymer adamantane-[poly(lactic-co-glycolic acid)-b-poly(N,N′-diethylaminoethyl methacrylate)-poly(ethylene glycol)monomethyl ether]4 was synthesized using adamantane as core.Self-assembly micelles of the synthesized polymer were prepared and the controlled release properties were further investigated.The results showed that the proportion of PDEAEMA had important effects on the properties of polymeric micelles,reflected by the fact that polymeric micelles with longer PDEAEMA segment had larger particle size,better drug loading capacity and higher cumulative drug release.Furthermore,the polymeric micelles had desired stability(CMC 0.0031 mg/mL),good pH-responsive function and high drug loading capacity(up to 24.8%).Under the simulated environment of tumor tissue(pH=5.0),the cumulative release of DOX-loaded micelles(85.2%)was significantly higher than those under the simulated environment of normal tissue(pH=7.4,20.9%),indicative of the well-controlled release behavior of drug-loaded micelles.In conclusion,such pHresponsive polymeric micelles 4sAd-PLGA-D-P present great potential in the field of anticancer drug delivery.