聚苹果酸-阿霉素/多烯紫杉醇纳米共聚物的制备及性质研究

Study on preparation and characterization of poly(β-malic-acid)-doxorubicin/docetaxel nanoconjugate

目的以聚苹果酸(PMLA)为载体,同时连接阿霉素(DOX)与多烯紫杉醇(DTX)制备纳米共聚物(PMLA-DOX/DTX),研究其体外释药及对肿瘤细胞的抑制作用。方法以"一锅煮"法同时连接DOX与DTX,HPLC法测定并计算载药率,动态透析法模拟体内释药,采用MDA-MB-231细胞筛选2种药物不同比例的协同效果,考察游离药物与纳米共聚物的细胞毒性和细胞摄取作用。结果 PMLA-DOX/DTX中DOX的载药率为21.5%±1.2%,DTX的载药率为11.03%±1.51%。共聚物体外释药稳定,无突释现象。细胞实验中2种药物在给药总质量浓度相同时,DOX与DTX摩尔比为10∶1时协同效果良好;MDA-MB-231细胞对纳米共聚物的摄取多于游离药物。结论 PMLA作为药物载体,同时递送化疗药物DOX与DTX,载药率高,可实现协同抗肿瘤作用。

Objective To synthesize polymer-drug conjugate based on poly（β-malic acid）（PMLA）bearing simultaneously doxorubicin（DOX）and docetaxel（DTX）and study the synergistic effect.Methods The method simultaneously conjugated DOX and DTX to mPEG-PMLA was a＂one pot＂method and the drug loading rates were determined by HPLC,simulation of drug release in vivo by dynamic dialysis.Dynamic dialysis was used to simulate drug release in vitro.MDA-MB-231 cells were used to study the synergistic effects and cellular uptake.Results The content of DOX in PMLA-DOX/DTX was 21.5%±1.2% and DTX was 11.03%±1.51%.In vitro cytotoxicity assay（human breast cancer cell,MDA-MB-231）,when the drug ratio was 10∶1,the synergistic effect was better.Dual drug-loaded conjugates could be easier to be internalized by the cells than free drugs.Conclusion PMLA delivered the chemotherapeutic drugs DOX and DTX simultaneously with high drug loading,which could tolerate the side effects with the efficient anti-tumor effect to make it a good candidate of nanocarrier.