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以一些独立机制为靶点的组合治疗系统可用于治疗肿瘤.本研究采用薄膜分散法结合pH梯度法制备包载阿霉素和去氢骆驼蓬碱的脂质体,进而构建组合递送系统.首先,建立简单、精确和准确的双波长紫外分光光度法测定脂质体中阿霉素和去氢骆驼蓬碱的含量,并进行了方法学验证.处方工艺研究中,分别优化了药脂比为1:20,载药时间为30分钟,载药温度为50℃.优化的脂质体平均粒径约为100 nm,多分散系数小于0.2,包封率高于93%.在pH 7.4的释放介质中两药物的释放十分缓慢,这预示着制剂具有良好的安全性.脂质体制剂中两个药物的协同性用MCF-7细胞的细胞毒实验来评价,研究结果表明,包载阿霉素和去氢骆驼蓬碱的脂质体协同指数达到0.81,表明具有显著的协同效应,可进一步增强体外抗增殖抑制作用活性.所有实验结果表明,上述两个脂质体的组合可成为有效的肿瘤治疗手段.“,”A combinatory therapeutic system that simultaneously targets several independent pathways is preferred for the treatment of cancer.In our study,a combinatory liposomal delivery system containing doxorubicin (Dox) and harmine (HM) was constructed by thin film dispersing method together with pH gradient method.A simple,precise and accurate spectrophotometric method for the determination of Dox and HM in liposomal formulation was established and validated.A drug HSPC ratio of 1:20,loading time of 30 min and loading temperature of 50 ℃ were the optimal conditions for the preparation of drug loaded liposomes,which exhibited excellent physicochemical properties such as average particle size of~100 nm,low polydispersity index below 0.2 and high entrapment efficiency above 93%.Sustained release of drug from liposomes at pH 7.4 showed good biological safety.The synergetic cytotoxic effect for these two drugs was evaluated in MCF-7 cells.The in vitro antitumor studies demonstrated the superior anti-proliferation activity of the liposomal Dox and HM with a combination index of 0.81,which indicated great synergistic effect and increased anti-proliferation efficiency.The experimental data suggested that combinational liposome therapy could be an effective way to develop efficient treatment of cancers.