Ratiometric delivery of doxorubicin and berberine by liposome enables superior therapeutic index than Doxil?  

作　　者：Ruoshi Zhang Yingxi Zhang Yue Zhang Xin Wang Xuanming Gao Yuyan Liu Xuanbo Zhang Zhonggui He Dun Wang Yongjun Wang 

机构地区：[1]Wuya College of Innovation,Shenyang Pharmaceutical University,Shenyang 110016,China [2]Department of Pharmaceutics,Shenyang Pharmaceutical University,Shenyang 110016,China [3]Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education,Shenyang Pharmaceutical University,Shenyang 110016,China

出　　处：《Asian Journal of Pharmaceutical Sciences》2020年第3期385-396,共12页亚洲药物制剂科学（英文）

基　　金：the Career Development Program for Yong and Middle-aged Teachers in Shenyang Pharmaceutical University。

摘　　要：Although the appearance of Doxil alleviated the cardiotoxicity of DOX, the progression-free survival of patients was not prolonged compared with traditional medication regimens, and side effects such as hand-foot syndrome has occurred. In order to solve this dilemma, we have designed a novel co-delivery strategy to construct a co-loaded liposome of berberine(BER) and doxorubicin(DOX), which was called Lipo Be Do. The optimal synergistic ratio of the two drugs was screened by cell cytotoxicity experiments in vitro, and the optimal attenuation ratio was further determined by in vivo cardiac H&E staining pathological sections. The optimal combination treatment caused a robust increase in apoptotic cells of 4T1, as compared to drug alone treatment. The prepared co-loaded liposome, Lipo Be Do, had high encapsulation efficiency and good stability. The nanoliposome carrier controlled the biological fate of the drugs and maintained a pre-defined optimal ratio in vivo. The Lipo Be Do significantly inhibited tumor growth in 4T1 murine mammary carcinoma model compared with Doxil(P < 0.05), and completely overcame the myocardial rupture toxicity caused by Doxil in mice. Our co-loaded liposome delivery platform technology provided a new direction for the clinical treatment of triple-negative breast cancer and the safe application of DOX.

关 键 词：BERBERINE DOXORUBICIN NANOLIPOSOMES Remote loading Combination therapy Cardiotoxity 

分 类 号：R943[医药卫生—药剂学]