中文摘要：

目的以泊洛沙姆407（P407）为载体,制备阿霉素-铜-姜黄素（DOX-Cu-Cur）三元配合物的纳米胶束,实现定量化联合载药和智能化释药,以期达到协同治疗效果。方法以P407为载体,采用Box-Behnken设计对制剂进行处方优化,并考察胶束的体外释药特性,MTT法研究胶束对肿瘤细胞的抑制作用。结果优化后的载药胶束（DOX-Cu-Cur/P407）粒径为（31.06±4.20）nm,多分散系数为0.174±0.028,阿霉素和姜黄素的包封率分别为（93.17±1.05）%、（100.03±1.10）%。体外释放曲线表明,胶束具有酸敏感释药特性,MTT结果表明DOX-Cu-Cur/P407能显著抑制肿瘤增殖,且较单一药物有更好的协同作用。结论 DOX-Cu-Cur/P407胶束具有均一的粒径和高包封率,能够响应肿瘤酸性微环境,有望实现定量化敏感释药和协同治疗效果。

英文摘要：

OBJECTIVE With Poloxamer 407（P407） as the carrier, doxorubicin-copper-curcumin ternary complex was en- capsulated in the micelles to achieve quantitative and intelligent drug release behavior and synergistic effect. METHODS With P407 as the carrier, the preparing technology was optimized by Box-Behnken design and the in vitro pH-sensitive drug release behavior of DOX-Cu-Cur/P407 was examined; the MTT analysis was carried out to evaluate the cytotoxicity to tumor cells. RESULTS Under the optimum condition, the encapsulation efficiency of doxorubicin and curcumin was （93.17 ± 1.05） and （100.03 ± 1.10）G, size distribution was （31.06 ± 4.20） nm, PDI is 0.174 ± 0.028. Meantime, in vitro drug release test showed the DOX-Cu-Cur/P407 micelles was pH-sensitive. The MTT analysis showed DOX-Cu-Cur/P407 micelles could significantly inhibit the tumor cells with a better synergistic effect compared with free drugs. CONCLUSION The optimal DOX-Cu-Cur/P407 micelle is uniform in size and has satisfactory encapsulation efficiency. Meanwhile it is sensitive to acidic microenvironment of tumor and can achieve the purpose of quantitative and intelligent drug release.