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荧光成像与药物控释双功能表阿霉素载药胶束的制备与体外评价

Preparation and in vitro evaluation of fluorescence imaging and drug controlled-release bifunctional epirubicin drug-loaded micelles
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摘要 目的制备荧光成像与药物控释双功能表阿霉素载药胶束(fluorescence imaging and drug controlled-release bifunctional epirubicin drug-loaded micelles,EPI-FIDCR)。研究EPI-FIDCR胶束的体外释放行为;初步评价EPI-FIDCR胶束在Hela细胞中的摄取及细胞毒性。方法采用薄膜分散法制备EPI-FIDCR胶束;以不同pH磷酸缓冲盐溶液(phosphate buffered saline,PBS)作为释放介质,评价EPI-FIDCR胶束的体外释放行为;通过MTT(3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide,thiazolyl blue tetrazolium bromide,MTT)法评价盐酸表阿霉素(epirubicin hydrochloride,EPI)、EPI-FIDCR胶束、聚乙二醇一聚乳酸嵌段共聚物(polyethylene glycol-polylactic acid block copolymers,PEG-PDLLA)及聚乙二醇修饰的石墨烯量子点(polyethylene glycol-modified graphene quantum dots,GQDs-PEG)的细胞毒性及测定IC50值;用荧光显微镜对EPI-FIDCR胶束在Hela细胞内的荧光成像进行研究。结果制备的EPI-FIDCR胶束平均粒径为(19.59±1.21)nm,Zeta电位为(-22.87±0.85)mV,包封率为(74.02±0.55)%,载药质量分数为(3.78±0.28)%,EPI-FIDCR胶束表现出缓释行为,通过计算分别得出EPI的IC50值为(5.54±0.06) mg·L-1,EPI-FIDCR胶束的IC50值为(7.03±0.03) mg·L-1。EPI-FIDCR胶束能够进入细胞,发挥荧光成像作用。结论成功制备了荧光成像与药物控释双功能表阿霉素载药胶束,具有较好应用前景。 Objective To prepare fluorescence imaging and drug controlled-release bifunctional epirubicin drug-loaded micelles(EPI-FIDCR).The in vitro release behavior of EPI-FIDCR was investigated.The uptake and cytotoxicity of EPI-FIDCR in Hela cells were preliminary evaluated.Methods EPI-FIDCR were prepared by thin-film dispersion method.The in vitro release behavior of EPI-FIDCR was evaluated by using different pH phosphate buffered saline(PBS) as release medium.The cytotoxicity of drug-loaded micelles,carrier and GQDs-PEG were evaluated by MTT method and the IC50 values were determined.The fluorescence imaging of EPI-FIDCR in Hela cells was studied by fluorescence microscopy.Results The average diameter of EPI-FIDCR was(19.59 ± 1.21) nm,the Zeta potential was(-22.87 ± 0.85) mV,the entrapment efficiency was(74.02 ± 0.55)% and the drug loading was(3.78 ± 0.28) %.The IC50 value of epirubichin hydrochloride(EPI) was(5.54 ± 0.06) mg·L-1 and the IC50 value of EPI-FIDCR was(7.03 ± 0.03) mg ·L-1.Micelles were able to enter the cell,and played a role in fluorescence imaging.Conclusion Fluorescence imaging and drug controlled-release bifunctional epirubicin drug-loaded micelles have been successfully prepared,which has a good prospect of application.
作者 韩星 李翔 张婧 房元英 金一 HAN Xing;LI Xiang;ZHANG Jing;FANG Yuanying;JIN Yi(State Key Laboratory of Innovative Medicine and Energy-saving and Reducing Consumption of Pharmaceutical Equipment,Jiangxi University of Traditional Chinese Medicine,Nanchang 330000,China;Ministry of Education Key Laboratory of Modern Chinese Medicines Preparation,Jiangxi University of Traditional Chinese Medicine,Nanchang 330000,China)
出处 《沈阳药科大学学报》 CAS CSCD 北大核心 2019年第3期187-194,242共9页 Journal of Shenyang Pharmaceutical University
基金 国家自然科学基金资助项目(81603054,81373347) 江西省杰出青年基金资助项目(20171BCB23097,20162BCB23034) 江西省青年科学基金重点资助项目(20171ACB21074) 江西省卫生厅中医药科研课题资助项目(2016A008).
关键词 聚合物胶束 聚乙二醇修饰的石墨烯量子点 药物递送 荧光成像 肿瘤治疗 polymeric micelles polyethylene glycol-modified graphene quantum dots drug delivery fluorescence imaging cancer therapy
作者简介 韩星(1993-),女(汉族),江西宜春人,硕士研究生,E-mail hanxing0904@foxmail.com;通讯作者:金一(1959-),男(朝鲜族),浙江杭州人,教授,博士,博士生导师,主要从事生物技术药物新剂型的研究工作,Tel.0791-87119650,E-mail jinyizju@hotmail.com;李翔(1981-),男(汉族),副教授,博士,主要从事中药新剂型与新技术的研究工作,Tel.0791-87119661,E-mailsterlinghawk@163.com。
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