原子转移自由基聚合调控制备两亲性嵌段共聚物纳米胶束及其载药性能

Study on Drug Loading Micelles of an Amphiphilic Block Copolymer Prepared Via ARGET ATRP

通过再生电子转移生成催化剂原子转移自由基聚合(ARGET ATRP)方法合成了PPEGMA-b-Pt BMA两亲性嵌段聚合物。首先,将甲基丙烯酸聚乙二醇酯(PEGMA)和2-溴异丁酸乙酯反应,在其链段端引入溴原子得到具有引发功能的大分子引发剂PPEGMA-Br;然后通过PPEGMA-Br引发甲基丙烯酸叔丁酯(t BMA)聚合,制备两亲性嵌段共聚物PPEGMA-b-Pt BMA。采用核磁共振(1H-NMR)对其化学结构进行表征,荧光探针法测定其临界胶束溶度。采用透射电子显微镜及激光粒度仪对制备的载药胶束的形态进行分析,研究了该胶束的载药量和包封率、载药胶束的释放行为。结果表明,PPEGMA-b-Pt BMA两亲性共聚物具有pH响应性,在pH值4.0条件下的释放速率明显高于pH值为7.4条件下的释放速率。载药及DOX释放研究表明,这种pH敏感的聚合物胶束是药物递送的良好载体。

The preparation of amphiphilic copolymer(PPEGMA-b-Pt BMA) was performed by activators regenerated by electron transfer atom transfer radical polymerization(ARGET ATRP). The macromolecular initiator(PPEGMA-Br) was fabricated via the reaction of Poly(ethylene glycol) methacrylate(PEGMA) and ethyl 2-bromoisobutyrate. Then, polyreaction of tert-butyl methacrylate(t BMA) and PPEGMA-Br obtained the amphiphilic block copolymer(PPEGMA-b-Pt BMA). The chemical structure of the copolymer was characterized by1 H-NMR, and the critical micelle solubility was determined by fluorescent probe. Moreover, the morphology of the DOX-loaded micelles was characterized by TEM and DLS. The DOX-loading capacity(LC), encapsulation efficiency(EE) and the release behavior of the DOX-loaded micelles were studied. The results show that the PPEGMA-b-Pt BMA is pH-responsive, and the release rate at pH 4.0 is significantly higher than the release rate at pH 7.4. Drug loading and DOX release findings suggest that this pH-sensitive polymer micelle is a favorable carrier in drug delivery field.