Faculty of Chemistry, Warsaw University of Technology, 3 Noakowskiego St., 00-664 Warsaw, Poland.
Faculty of Chemistry, Warsaw University of Technology, 3 Noakowskiego St., 00-664 Warsaw, Poland.
Int J Pharm. 2018 Mar 1;538(1-2):231-242. doi: 10.1016/j.ijpharm.2018.01.022. Epub 2018 Jan 16.
The aim of the present work was the synthesis and study the kinetics and profiles of camptothecin (CPT) release form block co- and ter-polymer conjugates comprising polylactide (PLA) segments and CPT moieties, structurally diverse by degrees of branching, content of d-PLA units and poly(ethylene glycol) methyl ether methacrylate (PEGMA). Six PLA, non-toxic macroinitiators (MIs), terminated with α-bromoester were synthesized. MIs were subjected to polymerization of CPT methacrylic derivative (CPTMA) with PEGMA at various ratios. The average contents of CPT from elemental analysis, NMR and UV-GPC were approximate to each other. The number of CPT molecules and PEGMA units was in the range of 9-195 and 0-280 per conjugate, respectively. PEGMA units plasticized PLA causing increase of its crystallinity, whereas 7% and more of d-PLA caused material amorphous. PEGMA units decreased thermal stability of conjugates, however it compatibillized the separated phases of PLA and PCPTMA, based on AFM. In vitro release rate of CPT from linear PLA conjugates deposited on injection-molded PLA bars increased by introduction of PEGMA units with zero-order kinetics and Korsmeyer-Peppas model indicating the super case II transport. Branched conjugates revealed some burst release and then the release was rather of first-order-kinetics with respect to CPT with non-Fickian transport.
本工作的目的是合成并研究包含聚丙交酯（PLA）段和喜树碱（CPT）部分的嵌段和接枝共聚物和三聚物缀合物中 CPT 的释放动力学和释放曲线，这些缀合物在支化程度、d-PLA 单元和聚乙二醇甲基醚甲基丙烯酸酯（PEGMA）的含量上结构不同。合成了六个 PLA 无毒大分子引发剂（MIs），其末端为α-溴代酯。将 MIs 与 PEGMA 进行 CPT 甲基丙烯酸酯（CPTMA）的聚合，比例不同。元素分析、NMR 和 UV-GPC 的 CPT 平均含量彼此相近。每个缀合物中 CPT 分子和 PEGMA 单元的数量分别为 9-195 个和 0-280 个。PEGMA 单元增塑 PLA，导致其结晶度增加，而 7%或更多的 d-PLA 则使材料无定形。PEGMA 单元降低了缀合物的热稳定性，但基于 AFM，它使 PLA 和 PCPTMA 的分离相相容。线性 PLA 缀合物沉积在注塑 PLA 棒上，CPT 的体外释放速率随着零级动力学和 Korsmeyer-Peppas 模型的 PEGMA 单元的引入而增加，表明超 II 型转运。支化缀合物先呈现出一定的突释，然后 CPT 的释放动力学更符合一级动力学，呈非菲克扩散。
