【作者】 庞志清； 冯亮； 华蓉蓉； 蒋新国；

【Author】 Zhiqing Pang,Liang Feng,Rongrong Hua,Xinguo Jiang School of Pharmacy,Fudan University,201203

【机构】 复旦大学药学院；

【摘要】 目的探讨乳铁蛋白修饰的载阿霉素/粉防已碱聚合物泡囊(Lf-PO-Dox/Tet)治疗脑胶质瘤的效果。方法立体定位注射C6细胞构建原位脑胶质瘤大鼠模型,考察Lf-PO-Dox/Tet的体内药动学和组织分布,评价其对脑胶质瘤的靶向递药特性;通过肿瘤体积大小的变化以及荷瘤大鼠的生存曲线评价其对脑胶质瘤的药效学。结果 Lf的修饰并未显著影响泡囊的长循环性能,各组泡囊在脾、肝蓄积较多,心、肾蓄积较少。脑内分布结果表明,Lf-PO-Dox/Tet可以进入脑组织并向肿瘤部位浓集。药效学结果表明植瘤14天后Lf-PO-Dox/Tet组的肿瘤体积显著低于其余各组;Lf-PO-Dox/Tet组荷瘤大鼠的中位生存期(31天)显著高于PO-Dox/Tet组(25天)、PO-Dox组(19天)和生理盐水组(17天),高于Lf-PO-Dox组(28天)。结论 Lf-PO-Dox/Tet在脑胶质瘤的治疗方面具有一定的潜力。更多还原

【Abstract】 Objective Chemotherapy of glioblastoma rats by lactoferrin-conjugated biodegradable polymersome holding doxorubicin and tetrandrine was explored. Method Glioma model was established by stereotactically injecting C6 cells into the right striatum of rats. Pharmacokinetics together with tissue distribution were investigated in C6 glioma implanted rats to evaluate the glioma delivery property. Tumor volume and survival time of glioma implanted rats treated with Lf-PO-Dox/Tet were determined to evaluate the anti-glioma effect. Results The pharmacokinetics revealed that the long circulation function of polymersomes was not significantly influenced by Lf conjugation. Brain distribution indicated that Lf-PO-Dox/Tet could enter the brain and accumulate in the tumour site. For other organs, polymersomes accumulated most in spleen and liver and relatively less in heart and kidney. Pharmacodynamics results demonstrated that tumor volume of glioma rats treated with Lf-PO-Dox/Tet was significantly smaller than other therapeutic groups, while the median survival time of rats treated with Lf-PO-Dox/Tet (31 days) was longer than Lf-PO-Dox (28 days) and significantly longer than the rest three therapeutic groups. Conclusion Lf-PO-Dox/Tet could have a therapeutic potential for glioma.更多还原