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。
Objective In order to achieve a controlled release profile of guest drugs from pore channels,enhance therapeutic effects and reduce the side effects,we constructed the redox-responsive drug delivery system in which mesoporous silica nanoparticles (MSNs) working as nanocarriers were modified with different amount of thiol groups.Methods The thiol-modified MSNs were prepared by using the postmodification method.The scanning electron microscope (SEM),transmission electron microscope (TEM) and BET and pore size analysis were employed to characterize the specific surface area,pore size and morphology of MSNs.The anti-cancer agent 6-mercaptopurine with thiolated groups working as a model drug was covalently loaded into MSNs by disulfide bonds.Results The drug loading efficiency of the nanocarriers could reach up to 5.02% with the addition of 1.00 m L MPTMS.The results of drug release experiment demonstrated that no premature release was observed from redox-responsive drug delivery system (MSN-SS-MP) based on mesoporous silica nanoparticles (MSNs) in the absence of GSH.However,the cumulative drug release reached above 70% within 2 h when the concentration of GSH was 3 mmol·L^(-1).Conclusions The covalently linked drug-loading delivery system exhibited distinct redox-responsive property,which provided a newidea for controlled drug release.
出处
《沈阳药科大学学报》
CSCD
北大核心
2017年第9期737-743,共7页
Journal of Shenyang Pharmaceutical University
基金
国家自然科学基金面上项目(81473165)
