可降解聚合物-阿霉素复合体局部给药治疗大鼠胶质肉瘤实验研究

Local delivery of biodegradable polymer-doxorubicin complex for the treatment of glioma in rats

目的本研究采用聚合物与阿霉素(DOX)结合成复合体,以验证是否其能够提高颅内胶质瘤模型鼠的生存期。方法混合溶解DOX和聚酸酐多聚体(pCPP-SA)后制备复合物,采用致死剂量的9L胶质肉瘤细胞系对40只Fisher 344大鼠行颅内注射制备大鼠胶质肉瘤模型。5 d后瘤腔内再行DOX复合物或空白复合物处理,比较不同组间大鼠生存时间及组织病理变化。结果相较于空白对照组及空白复合物处理组,接受DOX处理的大鼠生存时间明显增加,中位生存时间空白对照组为21 d,3%DOX处理组为34 d(P<0.01),5%DOX为45 d(P<0.0001)。结论 DOX具有显著抗肿瘤治疗效果,采用DOX复合物局部给药的方式能够显著延长生存时间,是对临床化疗给药途径提供有益补充。

Objective The effect of biodegradable polymer-doxorubicin complex on the survival time of intracranial glioma rats by local delivery drug system is investigated.Methods Polyanhydride polymers （PCPP-SA）,which contained Doxorubicin （DOX）,were manufactured by mix-melt method.A total of Fisher 344 rats received intracranial injection of 9L human gliosarcoma cells.Then the rats received DOX complex treatment or blank treatment 5 d later.The survival time and histological changes were examined to compare the changes among different groups.Results Comparing to the control group and blank-treatment group,the survival time for the DOX treatment was increased significantly.The median survival for the control group was 21 d,as 34 d in 3% DOX treatment group （P〈0.01）,and 45 d in 5% DOX treatment group（P〈0.0001）.Conclusion Doxorubicin is an effective antitumor agent for therapeutic treatment.Local delivery of polymer-doxorubicin complex can prolong the survival time and can be used as a promising adjunct to current therapeutic modalities.