还原响应型介孔二氧化硅-巯基嘌呤共价载药系统的构建与初步评价

发布时间：2019-01-01 17:03

【摘要】：目的为控制药物在到达作用部位前于载药系统的提前释放,提高疗效和降低毒副作用,研究制备了还原响应型介孔二氧化硅载药系统。方法采用后修饰法制备不同巯基化的介孔二氧化硅载体,通过扫描电镜、透射电镜及氮气吸附-脱附等手段对载体的外观形貌、比表面积及孔径分布进行表征,并选取具有巯基的抗癌药物6-巯基嘌呤作为模型药物,将药物通过二硫键共价装载到载体上。结果当巯基化试剂加入量为1 m L时,载药体系有最大的载药量为5.02%。研究所构建的还原响应型介孔二氧化硅载药系统,在没有谷胱甘肽(glutathione,GSH)存在的条件下,药物"零"释放,而当GSH的浓度为3 mmol·L~(-1)时,2 h累计释放量超过70%。结论研究构建的共价载药系统具有明显的还原响应型释药特征,为控制药物的释放提供了一个新的探索思路。
[Abstract]:Aim to control the release of the drug in the drug carrier system before reaching the site of action, to improve the efficacy and reduce the side effects, a reductive response mesoporous silica drug carrier system was prepared. Methods the mesoporous silica carriers with different sulfhydrylation were prepared by post-modification method. The morphology, specific surface area and pore size distribution of the carriers were characterized by scanning electron microscopy, transmission electron microscopy and nitrogen adsorption-desorption. The antitumor drug 6-mercaptopurine with sulfhydryl group was selected as the model drug, and the drug was covalently loaded into the carrier by disulfide bond. Results when the amount of mercapto reagent was 1 mL, the maximum drug loading was 5.02%. A reduction-responsive mesoporous silica drug carrier system was constructed. When the concentration of GSH was 3 mmol L ~ (-1), the drug was released "zero" in the absence of glutathione (glutathione,GSH). The accumulative release amount exceeded 70% in 2 h. Conclusion the covalent drug loading system has obvious characteristics of reductive response drug release, which provides a new approach for drug release control.
【作者单位】：沈阳药科大学药学院;沈阳医学院附属中心医院药剂科;
【基金】：国家自然科学基金面上项目(81473165)
【分类号】：R943

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