Zhao Yue, Lord Megan S, Stenzel Martina H
Centre for Advanced Macromolecular Design (CAMD), The University of New South Wales, Sydney, NSW 2052, Australia.
J Mater Chem B. 2013 Mar 21;1(11):1635-1643. doi: 10.1039/c3tb00360d. Epub 2013 Feb 5.
Cationic polymers are promising materials for the controlled delivery of heparin allowing the therapeutic delivery of growth factors bound to heparin. In this study, a series of block copolymers were prepared from oligo(ethylene glycol) methyl ether methacrylate (OEGMEMA) and 2-(methacryloyloxy)ethyl trimethyl ammonium chloride (METEA) via reversible addition-fragmentation chain transfer (RAFT) polymerization by varying the cationic block (METEA) from 5 to 54 units. Polyion complexes micelles between these block copolymers and heparin were formed. Their size could be systematically varied between 5 and 55 nm in size as well as -20 to +10 mV in overall charge by changing the cationic block length as well as the ratio of polymer to heparin. The polymer/heparin complexes did not impair the proliferation of human colon carcinoma cell line, WiDr, compared to cells exposed to medium only. The size of the cationic block copolymer as well as the ratio in which it was complexed with heparin influenced both heparin biological activity in a BaF32 cell assay as well as uptake into WiDr cells as determined by flow cytometry which demonstrated that the properties of the block copolymers can be tuned for various applications.
阳离子聚合物是用于肝素控释的有前景的材料，可实现与肝素结合的生长因子的治疗性递送。在本研究中，通过可逆加成-断裂链转移（RAFT）聚合反应，由甲基丙烯酸寡聚（乙二醇）甲醚（OEGMEMA）和2-（甲基丙烯酰氧基）乙基三甲基氯化铵（METEA）制备了一系列嵌段共聚物，其中阳离子嵌段（METEA）的单元数从5变化到54。这些嵌段共聚物与肝素之间形成了聚离子复合物胶束。通过改变阳离子嵌段长度以及聚合物与肝素的比例，它们的尺寸可以在5至55nm之间系统地变化，总电荷在-20至+10mV之间变化。与仅暴露于培养基的细胞相比，聚合物/肝素复合物不会损害人结肠癌细胞系WiDr的增殖。阳离子嵌段共聚物的尺寸以及其与肝素复合的比例，在BaF32细胞试验中影响肝素的生物活性，同时通过流式细胞术测定其对WiDr细胞的摄取，这表明嵌段共聚物的性质可针对各种应用进行调节。
