金属有机骨架材料的合成及其负载5-氟尿嘧啶的性质研究

发布时间：2018-02-14 10:39

本文关键词： 金属有机骨架材料 5-氟尿嘧啶药物缓释　出处：《沈阳师范大学》2017年硕士论文　论文类型：学位论文

【摘要】：金属有机骨架材料(metal organic frameworks,MOFs),是一类由金属离子或金属簇与有机配体连接在一起而形成的无线网络结晶材料。同传统的无机多孔材料相比,多孔金属有机骨架材料(MOFs)具有新颖的配位结构,多变的拓扑结构和许多潜在应用的优势,被广泛应用于吸附分离和药物的传递与释放等领域。5-氟上尿嘧啶(5-Fluorouracil,5-Fu)作为抗代谢抗肿瘤药物在临床广泛应用于多种肿瘤的治疗。但因该药半衰期短、毒副作用大等缺点而限制了在临床中的发展。为了克服此缺点,本文利用合成的三种结构不同的MOF材料,分别负载抗癌药物5-Fu并探究其载药性能及体外释放性能。本文以Fe和Zn作为中心金属,均三苯甲酸、对苯二甲酸和2-甲基咪唑为有机配体,经溶剂热法合成三种MOF材料,分别为MIL-100(Fe),MOF-5和ZIF-8。采用扫描电子显微镜、X射线粉末衍射、热重分析及红外光谱分析对其结构进行表征,研究三种金属有机骨架材料的外部形貌,骨架结构及其热稳定性等相关性能。采用紫外分光光度法为5-Fu的体外分析方法。载药结果表明,MOF与5-Fu的质量比和作用时间都会影响载药量,通过优化条件得到较高载药量。其中,MIL-100(Fe)的最高载药量为0.261 g/g载体;MOF-5的最高载药量为0.296 g/g载体;ZIF-8的最高载药量为0.505 g/g载体。对比载药前后的MOF载体,结构及稳定性并未发生变化,说明药物的填充并没有改变MOF原有的结构和性质。采用动态透析法进行体外释药实验,对三种MOF载体的体外释药进行了研究。体外释药曲线有明显的缓释效果,表明其可在长时间内持续释放药物,延长了作用时间也降低了给药次数。证明以金属有机骨架为载体负载5-Fu能提高5-Fu的抗肿瘤疗效和病变部位的局部药物浓度,可作为一种定位给药制剂,降低了5-Fu的毒性的同时提高了生物利用度。
[Abstract]:Metal-organic skeleton material, metal organic framework material, is a kind of wireless network crystalline material formed by metal ions or metal clusters connected with organic ligands. Porous metal-organic skeleton materials (MOFs) have novel coordination structures, variable topological structures and many potential applications. 5-Fluorouraciline (5-Fluorouraciline 5-Fuo) is widely used in the field of adsorption separation and drug delivery and release, as an antimetabolic antitumor drug, it has been widely used in the treatment of many kinds of tumors in clinic. However, because of its short half-life, the drug has a short half-life. In order to overcome this shortcoming, we use three kinds of MOF materials with different structure. In this paper, three kinds of MOF materials were synthesized by solvothermal method, using Fe and Zn as central metals, tribenzoic acid, terephthalic acid and 2-methyl imidazole as organic ligands respectively. The structures were characterized by scanning electron microscopy (SEM), thermogravimetric analysis (TGA) and infrared spectroscopy (IR), respectively. The external morphology of three kinds of metal and organic skeleton materials were studied. The in vitro analysis of 5-Fu by UV spectrophotometry showed that the mass ratio of MOF to 5-Fu and the time of action would affect the drug loading. The optimum conditions were used to obtain the higher drug load, in which the maximum drug loading capacity of MIL-100 (Fe) was 0.261 g / g / g carrier and the maximum load of MOF-5 was 0.296 g / g / g carrier ZIF-8 was 0.505g / g carrier. The structure and stability of MOF carrier before and after drug loading were not changed. The results showed that the drug filling did not change the original structure and properties of MOF. The in vitro drug release of three kinds of MOF carriers was studied by using dynamic dialysis method. The results showed that 5-Fu could continuously release the drug for a long time, prolong the action time and decrease the times of administration. It was proved that 5-Fu loaded with metal-organic skeleton as carrier could improve the antitumor effect of 5-Fu and the concentration of local drug in the lesion. It can be used as a drug delivery agent, which can reduce the toxicity of 5-Fu and improve the bioavailability of 5-Fu.
【学位授予单位】：沈阳师范大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O627;TQ460.1

【参考文献】