ZIF-8的制备及其在药物特征响应释放中的应用研究（0892退后重投）

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

摘要:

采用溶剂法合成了类沸石咪唑酯骨架材料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结构和性能的影响。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的载药及特征响应释放性能。结果表明：以去离子水、甲醇和正辛醇为溶剂均可得到结晶度高的纯相ZIF-8微粒，但以去离子水为溶剂时，需加入三乙胺来促进配体的去质子化；在实验配比情况下，在室温（25℃）条件下可获得较理想的产率；浊度检测表明3h后，反应进程达到80%。合成的ZIF-8均具有良好的热稳定性，但呈现明显酸不稳定性。实验合成的ZIF-8纳米微粒载药效率最高可达19.73%，体外溶出实验表明其在酸性环境中释放效率明显快于中性环境中的释放效率，呈现明显的特征响应释放性能。

Abstract:

The nano-particles of Zeolitic Imidazolate Frameworks ZIF-8 were prepared by solvent process, and the effects of reaction solvent, temperature and time on the structure and properties of ZIF-8 were investigated systematically. Then the synthetic ZIF-8 particles were used as the carrier of the anti-cancer drug doxorubicin hydrochloride (DOX), and the dissolution in vitro were studied. The results showed that the nano-particles of high crystallinity could be obtained in the solvent of methanol, n-octanol or deionized water, respectively. But in the case of deionized water, the triethylamine needed to be added to promote the deprotonation of Ligands. The optimized yield was achieved at the temperature of 25℃, and the 80% of the reaction processes were completed in the initial 3 hours determined by the turbidity. The synthetic nano-particles had good hydrothermal stability, and were sensitive to the acid environment. The drug loading efficiencies for DOX were from 16% to 20%, and the speed of the dissolution in vitro was faster obviously in acid environment than it in the neutral environment.