巯嘌呤/维拉帕米-介孔氧化硅释药系统的构建及逆转耐药活性研究

6-Mercaptopurine/verapamil-mesoporous silica and reversing multidrug resistance

目的制备巯嘌呤/维拉帕米-介孔氧化硅释药系统并评价其逆转耐药作用。方法采用共缩聚法合成介孔氧化硅纳米粒并载药,制备巯嘌呤/维拉帕米-介孔氧化硅释药系统;动态透析法研究该释药系统的体外释药特性;噻唑蓝比色法(MTT法)评价该释药系统的逆转耐药作用及可能机制。结果所制备释药系统的粒径在170~250 nm左右,Zeta电位在-30 m V^-40 m V,微观形态呈球形,均匀分布,具有规则介孔孔道。体外释放显示维拉帕米缓慢释放,6-巯嘌呤加入诱导剂之前无释放,加入诱导剂后释药过程呈现先突释后缓释。MTT法检测显示所制备释药系统与阳性药维拉帕米及同浓度物理混合物相比,具有显著逆转耐药作用。结论所制备的巯嘌呤/维拉帕米-介孔氧化硅释药系统有较好的抗肿瘤活性及逆转耐药作用。

Objective To prepare 6-mercaptopurine/verapamil-loaded mesoporous silica, to examine its in vitro antitumor activity and to evaluate if it can reverse drug-resistance. Methods The mesoporous silica nanoparticles（ MSNS） were synthesized with copolycondensation method. Separately loaded 6-mercaptopurine and verapamil onto MSNS to construct 6-mercaptopurine/verapamil-mesoporous silica. Dynamic dialysis was used to analyze the in vitro drug release. The reversal of drug resistance of 6-mercaptopurine/verapamil-mesoporous silica was evaluated on MCF-7 and MCF-7/ADM cells using MTT assay. Results There are spherical microstructure, uniform distribution and regular mesoporous channels in the prepared carrier system with a grain diameter ranging from 170 nm to 250 nm and the Zeta potential was in the range of -30 mV to -40 mV. The in vitro drug release showed that no 6-mercaptopurine be released before the addition of DTT but 6-mercaptopurine was suddenly and then slowly released with the addition of DTT. The results of MTT assays showed that 6-mercaptopurine/verapamil-mesoporous silica carrier system had a good effect on the reversal of drug-resistance. Conclusion 6-mercaptopurine/verapamil-mesoporous silica carrier system has a good antitumor activity and can reverse drug resistance.