共载吴茱萸碱及磷酸氯喹复方脂质体的制备及乳腺癌抗癌效果初步研究  

Pilot Study on the Preparation of EVO-CQ-Lips and Its Anti-cancer Effect on Breast Cancer

作　　者：杨成莉 文志鹏 李明 郑志昌 Yang Chengli;Wen Zhipeng;Li Ming;Zheng Zhichang(Department of Pharmacy,the Affiliated Hospital of Guizhou Medical University,Guiyang 550000,Guizhou,China)

机构地区：[1]贵州医科大学附属医院药剂科,贵阳550000

出　　处：《肿瘤预防与治疗》2022年第2期93-101,共9页Journal of Cancer Control And Treatment

基　　金：国家自然科学基金(编号:81860543);贵州省中医药管理局中医药民族医药科学技术研究课题(编号:QZYY-2016-017)。

摘　　要：目的:制备双载吴茱萸碱及磷酸氯喹复方脂质体(EVO-CQ-Lips),并研究其体外抗乳腺癌细胞增殖的活性。方法:首先采用薄膜分散法制备载吴茱萸碱(evodiamine, EVO)脂质体,然后通过硫酸铵梯度法共载入磷酸氯喹(chloroquine, CQ)。采用单因素结合正交设计筛选最优处方,并对最优处方粒径、包封率、载药量、外观形态进行表征,并考察其储存稳定性、体外抑制释放、体外乳腺癌细胞MCF-7增殖等情况。结果:所制备EVO-CQ-Lips外观形态为类球形,粒径为(170±6.24)nm, EVO的包封率为59.22%±4.52%、载药量为6.59%±1.38%,CQ的包封率为76.29%±1.02%、载药量10.03%±0.31%。体外稳定性良好,且对正常细胞毒性较低,生物安全性良好。体外释放结果显示EVO及CQ释放率均能达到80%以上,具有良好的缓释效果。MTT结果显示EVO-CQ-Lips对MCF-7细胞具有良好的抗乳腺癌活性。活死细胞染色结果显示纳米粒对MCF-7细胞杀伤效果良好且呈浓度依赖性。结论:本研究成功制备载CQ及EVO脂质体,且其具有良好的体外抗乳腺癌活性。Objective:To prepare EVO-CQ-Lips[liposomes loaded with chloroquine(CQ)and evodiamine(EVO)],and study its inhibited poliferation of breast cancer cells in vitro.Methods:Liposome-encapsulated EVO was prepared by the film dispersion method,and further loaded with CQ by the ammonium sulfate gradient method.The optimal prescription was screened by single factor combined with orthogonal designs,and was characterized by particle size,encapsulation efficiency and drug loading rate;its storage stability,releasing and inhibition of breast cancer cell proliferation were investigated in vitro.Results:The prepared EVO-CQ-Lips were spherical particles,with a size of(170±6.24)nm.The encapsulation efficiency and drug loading capacity for EVO and CQ were[(59.22±4.52)%vs(76.29±1.02)%and(6.59±1.38)%vs(10.03±0.31)%],respectively.The in vitro experiment showed that EVO-CQ-Lips had good stability and biosafety,and is non-toxic to normal cells;both EVO and CQ had good sustained-release effect,with a release rate above 80%.MTT assay showed that EVO-CQ-Lips had good anticancer effect on breast cancer cells(MCF-7).Cell proliferation and cytotoxic-ity assays showed that EVO-CQ-Lips nanoparticles had concentration-dependent cancer-killing effect(MCF-7).Conclusion:In this study,double-loaded liposomes with CQ and EVO are successfully prepared and shows good anti-breast cancer activity in vitro.

关 键 词：EVO-CQ-Lips 乳腺癌 处方优化 药物释放 增殖抑制 

分 类 号：R737.9[医药卫生—肿瘤] R965[医药卫生—临床医学]