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共载吡柔比星和长春瑞宾混合胶束的构建及其对乳腺癌的治疗研究
引用本文:陈丹,周红利,赵婷,郭晨琦,张荣苹,李佳,龚涛. 共载吡柔比星和长春瑞宾混合胶束的构建及其对乳腺癌的治疗研究[J]. 四川大学学报(医学版), 2021, 52(4): 612-618. DOI: 10.12182/20210760105
作者姓名:陈丹  周红利  赵婷  郭晨琦  张荣苹  李佳  龚涛
作者单位:四川大学华西药学院 靶向药物与释药系统教育部重点实验室 成都 610041;四川大学华西口腔医院 成都 610041
基金项目:国家自然科学基金(No. 81872804)资助
摘    要:目的 研究使用硫酸软骨素-胆固醇聚合物(CS-Chol)和二硬脂酰基磷脂酰乙醇胺-聚乙二醇(DSPE-mPEG2000)构建一种共载吡柔比星(pirarubicin,THP)和长春瑞宾(vinorelbine,VRL)的混合胶束(T+V-CS胶束),并对其治疗乳腺癌的效果进行评价.方法 用超声-透析法制备T+V-CS胶...

关 键 词:吡柔比星  长春瑞宾  胶束  乳腺癌  药效学
收稿时间:2021-02-01

Co-delivery of Pirarubicin and Vinorelbine by Micelles for the Treatment of Breast Cancer
CHEN Dan,ZHOU Hong-li,ZHAO Ting,GUO Chen-qi,ZHANG Rong-ping,LI Jia,GONG Tao. Co-delivery of Pirarubicin and Vinorelbine by Micelles for the Treatment of Breast Cancer[J]. Journal of Sichuan University. Medical science edition, 2021, 52(4): 612-618. DOI: 10.12182/20210760105
Authors:CHEN Dan  ZHOU Hong-li  ZHAO Ting  GUO Chen-qi  ZHANG Rong-ping  LI Jia  GONG Tao
Affiliation:1.Key Laboratory of Drug Targeting and Delivery System of the Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
Abstract:  Objective  To develop a pirarubicin (THP) and vinorelbine (VRL) codelivery nano-micellar system (T+V-CS micelles) of pirarubicin (THP) and vinorelbine (VRL) by using chondroitin sulfate-cholesterol polymers (CS-Chol) and DSPE-mPEG2000 and to evaluate the therapeutic efficacy of the codelivery nano-micelles in breast cancer treatment.  Methods  T+V-CS micelles were prepared by ultrasonic-dialysis method, and the physicochemical characterization were evaluated using multiple technological means. The anti-tumor efficacy of T+V-CS micelles in vitro was evaluated by MTT assay and cell cycle arrest analysis. Evaluation of the therapeutic effect of T+V-CS micelles in vivo was carried out on xenograft 4T1 murine breast cancer bearing BALB/c mice model.  Results  T+V-CS micelles displayed a nearly spherical shape when observed through transmission electron microscope. The particle size and polydispersity indexes (PDI) of T+V-CS micelles was (155.5±4.5) nm and 0.170±0.003 respectively, while the Zeta potential was (?23.0±0.9) mV. Meanwhile, T+V-CS micelles demonstrated high encapsulation efficiency of (81.87±2.56)% for THP and (87.54±2.82)% for VRL and a high overall drug loading efficiency of (10.20±1.20)%. In vitro and in vivo studies of the therapeutic efficacy of breast cancer showed that T+V-CS micelles had synergistic anti-tumor effect and induced increased G2/M cell cycle arrest in 4T1 cells, which could significantly inhibit tumor growth and prolong survival compared with the therapeutic efficacy of micelles loaded with a single kind of drug or free drug solutions.  Conclusion  The study showed that T+V-CS micelles had excellent anti-tumor effect, offering a reference to the clinical treatment of breast cancer.
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