热响应全氟聚醚丙烯酸酯共聚物的制备及载药性能

Preparation and drug loading properties of thermally responsive perfluoropolyether acrylate copolymer

以甲基丙烯酸羟乙酯(HEMA)和全氟聚醚酰氟(HFPO)反应生成的全氟聚醚酰氟甲基丙烯酸羟乙酯(PFPHM)为疏水内核,N,N-二甲基丙烯酰胺(DMAA)为热响应功能段,聚乙二醇甲基丙烯酸酯(PEGMA_(360))为亲水外壳,通过3次原子转移自由基聚合反应制备出热响应聚合物[P(PFPHM9-b-DMAA-b-PEGMA_(360))],考察了其对盐酸阿霉素(DOX/HCl)的载药性能。通过^(19)FNMR、^(1)HNMR、FTIR、DLS、UV-Vis、激光共聚焦显微镜和荧光分光光度计对其化学结构、临界胶束浓度(CMC)、最低临界溶解温度(LCST)、生物毒性、胶束稳定性及载药性能进行了研究。结果表明,P(PFPHM9-b-DMAA-b-PEGMA_(360))的CMC为1.0μg/m L,LCST为38.7℃,胶束稳定性良好,载药量为20.6%,包封率为86.6%,在42和37℃下,72 h的累积释药率分别为91.9%和35.4%,表明P(PFPHM9-b-DMAA-b-PEGMA_(360))具有热响应性,作为DOX/HCl物载体具有很大潜力。

Thermally responsive polymer[P(PFPHM9-b-DMAA-b-PEGMA_(360))]was prepared by atom transfer radical polymerization using perfluoropolyetheryl fluoromethyl acrylate(PFPHM)synthesized from hydroxyethyl methacrylate(HEMA)and hexafluoropropylene oxide(HFPO)as hydrophobic core,N,N-dimethylacrylamide as thermal response function segment,and poly(polyethylene glycol methacrylate_(360))as hydrophilic shell.Then,its DOX/HCl drug loading properties was investigated.The chemical structure,critical micelle concentration(CMC),lower critical solution temperature(LCST),biological toxicity,stability of micelles and drug loading properties were characterized and analyzed by ^(19)FNMR,^(1)HNMR,FTIR,DLS,UV-Vis,laser confocal microscopy and fluorescence spectrophotometer.The results showed that P(PFPHM9-b-DMAA-b-PEGMA_(360))exhibited a CMC of 1.0μg/mL,LCST of 38.7℃and excellent micelle stability.Moreover,analysis of drug loading indicated that the polymer displayed a drug loading capacity for DOX/HCl of 20.6%,encapsulation rate of 86.6%,and 72 h cumulative drug release rate at 42 and 37℃ were 91.9% and 35.4%,respectively,which suggested that P(PFPHM9-b-DMAA-b-PEGMA_(360))was temperature sensitive and had great potential as a drug carrier for DOX/HCl.