摘要
以透明质酸为载体,采用全化学合成法构建谷胱甘肽敏感的巯嘌呤-透明质酸(6-MP-ss-HA)高分子前药,对目标产物的结构进行鉴定,并探讨了物料投料比、温度和反应介质等条件对产率的影响.在30℃下以乙腈为反应介质,且巯嘌呤(6-MP)与I2按摩尔比1∶1投料时,巯嘌呤-ss-巯嘌呤(6-MP-ss-6-MP)的产率可达84.3%.模拟血液和细胞内环境研究该前药对谷胱甘肽的响应性释药性能,结果表明,药物累积释放率与谷胱甘肽浓度正相关,且基本只在细胞内释放药物.
A glutathione(GSH)-sensitive polymeric prodrug(6-MP-ss-HA)was constructed with hyaluronic acid(HA)as a carrier by chemical total synthesis and the factors impacting on the yield of the reaction were investigated including ratio of reactants,temperatures and solvents.The yield of mercaptopurine-ss-mercaptopurine(6-MP-ss-6-MP)reached 84.3% with the molar ratio of I2 to mercaptopurine 1∶1at 30℃in acetonitrile.The molecular structure of the compounds had been characterized by 1 H NMR and IR.Our experiment simulated the blood and intracellular environment to study the interaction between the drug release of 6-MP-ss-HA and the concentration of GSH.The results of glutathione dependent release show that the accumulation of the drug release rate is positively correlated with the concentration of GSH and the drug is released mainly within the cells.
引文
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