Page 39 - 精细化工2019年第9期

第 36 卷第 9 期 精 细 化 工 Vol.36, No.9
201 9 年 9 月 FINE CHEMICALS Sept. 2019

功能材料
ZIF-8 的制备及其在药物特征响应释放中的应用

*
刘 策，王志祥，武法文
（中国药科大学 工学院，江苏 南京 211198）

摘要：以硝酸锌和 2-甲基咪唑为原料，采用溶剂法合成了 ZIF-8 纳米微粒，考察了反应溶剂、反应温度和反应
时间等因素对其产率、结构和性能的影响。并以合成的 ZIF-8 纳米微粒作为药物载体，研究了其对抗癌药物盐
酸阿霉素（DOX）的载药及酸响应释放性能。结果表明，溶剂的质子化能力对 ZIF-8 微粒的结构和形貌有明显
影响，以质子化能力适中的甲醇作反应溶剂可获得粒径大小均一、形貌规整的微粒；以甲醇为溶剂，在硝酸锌
和 2-甲基咪唑的物质的量比为 1∶4、25 ℃下反应 24 h 时，ZIF-8 产率可达 36%；浊度检测表明，以反应 48 h
的浊度为基准，反应 3 h 时，反应进程达到 80%。合成的 ZIF-8 微粒均具有良好的热稳定性，但呈现明显酸不稳
定性。制备的 ZIF-8 纳米微粒载药效率最高可达 19.73%，体外溶出实验表明，DOX@ZIF-8 在酸性环境中释放
效率明显快于在中性环境中的释放效率，呈现出优异的酸响应释放性能。
关键词：ZIF-8；质子化；盐酸阿霉素；药物吸附；响应释放；功能材料
中图分类号：TQ460.4 文献标识码：A 文章编号：1003-5214 (2019) 09-1767-07

Preparation of Zeolitic Imidazolate Frameworks ZIF-8 and
Its Application in the Drug Response Release

*
LIU Ce, WANG Zhi-xiang, WU Fa-wen
（School of Engineering, China Pharmaceutical University, Nanjing 211198, Jiangsu, China）

Abstract: Zeolitic imidazolate frameworks-8 (ZIF-8) nanoparticles were prepared from zinc nitrate and
2-methylimidazole by solvent process. The effects of solvent, reaction temperature and reaction time on the
yield, structure and properties of ZIF-8 were investigated systematically. Subsequently, the synthesized
ZIF-8 nanoparticles were used as carrier of anti-cancer drug doxorubicin hydrochloride (DOX), and the
drug loading and acid release of DOX were studied. The results showed that the protonation of solvent had
an obvious effect on the structure and morphology of ZIF-8 nanoparticles. The ZIF-8 particles with uniform
size and regular morphology could be obtained using methanol as solvent. Under the conditions of molar
ratio of zinc nitrate to 2-methylimidazole 1∶4 with methanol as solvent, the yield of ZIF-8 was up to 36%
at the temperature of 25 ℃ for 24 h. And the 80% of the reaction processes were completed in the initial 3
h compared with the turbidity at the 48 h. The synthetic nanoparticles had good hydrothermal stability, but
showed obvious acid instability. The drug loading capacity for DOX was 19.73%. In vitro dissolution
experiments showed that the release efficiency of DOX@ZIF-8 in acid environment was obviously faster
than that in the neutral environment, indicating that the prepared ZIF-8 nanoparticles had excellent acid
response release property.
Key words: ZIF-8; protonation; doxorubicin hydrochloride; drug adsorption; response release; functional
materials

在抗肿瘤药物的研发应用过程中，一个亟需解 伤害，因此靶向释放或定向给药成为抗肿瘤药物研
决的问题是如何减少抗肿瘤药物对正常组织细胞的 究的热点和发展趋势 [1-4] 。其中，寻找出绿色无毒、

收稿日期：2019-01-23; 定用日期：2019-03-30; DOI: 10.13550/j.jxhg.20190084
基金项目：中央高校基本科研业务费（中国药科大学 2016ZPY004）
作者简介：刘 策（1993—），男，硕士生。联系人：武法文（1976—），男，副教授，E-mail：wufawen@cpu.edu.cn。