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
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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IC_(50)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IC_(50)值为(5.54±0.06) mg·L~(-1),EPI-FIDCR胶束的IC_(50)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 IC_(50) 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 IC_(50) value of epirubichin hydrochloride(EPI) was(5.54 ± 0.06) mg·L~(-1) and the IC_(50) 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.
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 IC_(50) 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 IC_(50) value of epirubichin hydrochloride(EPI) was(5.54 ± 0.06) mg·L~(-1) and the IC_(50) 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.
引文
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[2] TARIQ M,ALAM M A,SINGH A T,et al.Surface decorated nanoparticles as surrogate carriers for improved transport and absorption of epirubicin across the gastrointestinal tract:pharmacokinetic and pharmacodynamic investigations[J].Int J Pharm,2016,501(1/2):18-31
[3] XIONG H X,DIAO Q P,JIN R,et al.Synthesis and application of thiol-functionalized magnetic nanoparticles for studying interactions of epirubicin hydrochloride with bovine serum albumin by fluorescence spectrometry[J].Luminescence,2017,32(2):142-148.
[4] 汤佳明,赵修华,祖元刚.盐酸表阿霉素纳米靶向制剂的缓释效应[J].中国组织工程研究,2013,17(21):3846-3853.
[5] NASRA M,NAFEEB N,SAADA H,et al.Improved antitumor activity and reduced cardiotoxicity of epirubicin using hepatocyte-targeted nanoparticles combined with tocotrienols against hepatocellular carcinoma in mice.[J].Eur J Pharm Biopharm,2014,88 (1):216-225.
[6] CHAUHAN V P,JAIN R K.Strategies for advancing cancer nanomedicine[J].Nat Mater,2013,12(11):958-962.
[7] KALLURU P,VANKAYALA R,CHIANG C S,et al.Nano-graphene oxide-mediated in vivo fluorescence imaging and bimodal photodynamic and photothermal destruction of tumors[J].Biomaterials,2016,95:1-10.
[8] TAVARES A,CHONG L,PETRYAYEVA E,et al .Quantum dots as contrast agents for in vivo tumor imaging:progress and issues[J].Anal Bioanal Chem,2011,399(7):2331-2342.
[9] 李晓然,袁晓燕.聚乙二醇-聚乳酸共聚物药物载体[J].化学进展,2007,19(6):973-981.
[10] DONG J,WANG K Q,SUN L,et al.Application of graphene quantum dots for simultaneous fluorescence imaging and tumor-targeted drug delivery[J].Sensor Actuat B-Chem,2018,256:616-623.