TMZ@ZIF-8纳米粒的制备、表征及体内外抗肿瘤研究  

TMZ@ZIF-8 nanoparticles:preparation,characterization,and in vivo and in vitro anti-tumor studies

作　　者：刘婷 王怡 李冰辉 何硕 夏江 朱婷 LIU Ting;WANG Yi;LI Binghui;HE Shuo;XIA Jiang;ZHU Ting(School of Pharmacy,Harbin University of Commerce,Harbin 150076,China;College of Pharmacy,Harbin Medical University,Heilongjiang Daqing 163319,China;Honors’School,Harbin University of Commerce,Harbin 150028,China;Center of Pharmaceutical Engineering and Technology,College of Pharmacy,Harbin University of Commerce,Harbin 150076,China)

机构地区：[1]哈尔滨商业大学药学院,哈尔滨150076 [2]哈尔滨医科大学药学院,黑龙江大庆163319 [3]哈尔滨商业大学英才学院,哈尔滨150028 [4]哈尔滨商业大学药学院药物工程技术研究中心,哈尔滨150076

出　　处：《中国药房》2024年第9期1100-1107,共8页China Pharmacy

基　　金：黑龙江省中医药管理局中医药科研课题(No.ZHY2023-211,No.ZHY2023-210);2023年度哈尔滨商业大学“青年科研创新人才”培育计划(No.2023-KYYWF-1028);哈尔滨商业大学博士后科研启动项目(No.BS0087);哈尔滨商业大学博士科研支持计划(No.22BQ46,No.22BQ57)。

摘　　要：目的制备沸石咪唑骨架(ZIF)-8纳米粒(NPs)负载替莫唑胺(TMZ)(简称TMZ@ZIF-8 NPs)药物递送系统,以增加药物在病灶的富集和抗脑胶质瘤效果。方法采用室温溶液反应法制备ZIF-8 NPs后,再采用浸渍法制备TMZ@ZIF-8 NPs药物递送系统。进行透射电镜、激光粒度及傅里叶变换红外光谱等表征和溶出实验,并进行体外及体内抗肿瘤活性实验。结果TMZ@ZIF-8 NPs制备成功,粒径为(126.23±7.92)nm,载药率为(28.79±1.26)%,72 h累积溶出速率为(72.36±3.62)%。体外抗肿瘤活性实验结果显示,ZIF-8 NPs的相对细胞存活率一直保持在90%以上;与游离的TMZ相比,TMZ@ZIF-8 NPs对C6细胞的生长、增殖表现出更优的抑制作用、更高的被摄取能力和更好的促凋亡效果。体内抗肿瘤活性实验结果显示,ZIF-8 NPs在大鼠脑部不富集,TMZ在脑部富集效果并不显著,而TMZ@ZIF-8 NPs在脑部富集效果显著。结论ZIF-8 NPs可有效负载TMZ,制备成功的TMZ@ZIF-8可提高TMZ摄取能力及抗脑胶质瘤效果。OBJECTIVE To prepare zeolite imidazole framework(ZIF)-8 nanoparticles(NPs)loaded with temozolomide(TMZ)(abbreviated as TMZ@ZIF-8 NPs)drug delivery system,thus increasing drug enrichment and anti-glioma effects in lesions.METHODS After preparing ZIF-8 NPs using the room temperature solution reaction method,the impregnation method was used to prepare TMZ@ZIF-8 NPs drug delivery system.Characterization was carried out using transmission electron microscopy,laser particle size,and Fourier transform infrared spectroscopy,and dissolution and anti-tumor activity experiments in vitro and in vivo were conducted.RESULTS TMZ@ZIF-8 NPs were successfully prepared with the particle size of(126.23±7.92)nm,drug loading amount of(28.79±1.26)%,and 72 h cumulative dissolution rate of(72.36±3.62)%.The results of in vitro anti-tumor activity experiments showed that the relative cell survival rate of ZIF-8 NPs remained above 90%;the prepared TMZ@ZIF-8 NPs delivery system exhibited superior inhibition,higher uptake capacity,and better promoting apoptosis effects on the growth and proliferation of C6 cells as compared with the free TMZ.The results of in vivo anti-tumor activity experiments showed that ZIF-8 NPs were not enriched in the brain of rats,and the enrichment effect of TMZ in the brain was not significant,while TMZ@ZIF-8 NPs had a significant enrichment effect in the brain.CONCLUSIONS ZIF-8 NPs can effectively load TMZ,and successfully prepared TMZ@ZIF-8 NPs can improve TMZ uptake ability and anti-glioma effect.

关 键 词：替莫唑胺 沸石咪唑骨架 PH敏感 脑胶质瘤 药物递送系统 纳米粒 

分 类 号：TQ460.4[化学工程—制药化工] R943[医药卫生—药剂学]