含葡糖基酮洛芬乙烯醇酯共聚物的合成及其药物释放性能

分别利用化学法和酶促法合成了酮洛芬乙烯酯和葡萄糖丁二酸乙烯酯(6-O-乙烯丁二酰-D-葡萄糖)2种聚合单体,通过2种单体的自由基聚合反应制备了具有较高分子量的酮洛芬葡萄糖共聚物前药,通过IR、NMR对聚合物的结构进行了表征,用GPC方法测定共聚物分子量。研究了聚合单体投料比例对共聚物分子量和载药量的影响。结果表明,随着药物乙烯酯在投料中比例的增加,聚合物前药的分子量逐渐下降,聚合物中酮洛芬的载药量逐渐增加。酮洛芬含糖聚合物前药的体外释放研究表明,酮洛芬的释放时间大大延长,达到了缓释的目的,释药速率随着聚合物前药中葡萄糖含量增加而加快。聚合物前药的释放动力学模拟结果显示,共聚物释药更符合一级动力学释放模型。

Preparation and Sustained-release of Ketoprofen Polymeric Prodrug with Glucose Pendant

An enzymatic synthesis and chemical polymerization strategy has been used to prepare ketoprofen polymeric prodrug with glucose pendant. Polymerizable ketoprofen vinyl ester(KVE) and glucose derivative(6-O-vinylsuccinoyl-D-glucose)(VSUG) were obtained. Then, polymeric prodrugs of ketoprofen were synthesized by the two kinds of monomers with different molar ratios(n(KVE)∶n(VSUG): 1∶1, 1∶2, 2∶1, 4∶1) through free radical reaction using AIBN as the initiator. The structures of products were confirmed by IR, NMR, and GPC. The results suggested that the molecular weight decreased and drug loading capacity increased as the ratio of KVE in the feed raised. In vitro release behavior of these copolymers was investigated in PBS(pH=7.4) at 37 ℃. Contrast to the parent drug, the outcome demonstrated that the polymeric prodrug could effectively prolong the drug release rate. And the release rate of ketoprofen from polymeric prodrugs increased with the raising of glucose in the polymeric prodrug. Furthermore, investigations of the drug release profiles and kinetics suggested that the drug release gave a good fit to first order kinetic model.