本文關(guān)鍵詞： 金屬有機(jī)骨架材料 5-氟尿嘧啶 藥物緩釋　出處：《沈陽師范大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：金屬有機(jī)骨架材料(metal organic frameworks,MOFs),是一類由金屬離子或金屬簇與有機(jī)配體連接在一起而形成的無線網(wǎng)絡(luò)結(jié)晶材料。同傳統(tǒng)的無機(jī)多孔材料相比,多孔金屬有機(jī)骨架材料(MOFs)具有新穎的配位結(jié)構(gòu),多變的拓?fù)浣Y(jié)構(gòu)和許多潛在應(yīng)用的優(yōu)勢(shì),被廣泛應(yīng)用于吸附分離和藥物的傳遞與釋放等領(lǐng)域。5-氟上尿嘧啶(5-Fluorouracil,5-Fu)作為抗代謝抗腫瘤藥物在臨床廣泛應(yīng)用于多種腫瘤的治療。但因該藥半衰期短、毒副作用大等缺點(diǎn)而限制了在臨床中的發(fā)展。為了克服此缺點(diǎn),本文利用合成的三種結(jié)構(gòu)不同的MOF材料,分別負(fù)載抗癌藥物5-Fu并探究其載藥性能及體外釋放性能。本文以Fe和Zn作為中心金屬,均三苯甲酸、對(duì)苯二甲酸和2-甲基咪唑?yàn)橛袡C(jī)配體,經(jīng)溶劑熱法合成三種MOF材料,分別為MIL-100(Fe),MOF-5和ZIF-8。采用掃描電子顯微鏡、X射線粉末衍射、熱重分析及紅外光譜分析對(duì)其結(jié)構(gòu)進(jìn)行表征,研究三種金屬有機(jī)骨架材料的外部形貌,骨架結(jié)構(gòu)及其熱穩(wěn)定性等相關(guān)性能。采用紫外分光光度法為5-Fu的體外分析方法。載藥結(jié)果表明,MOF與5-Fu的質(zhì)量比和作用時(shí)間都會(huì)影響載藥量,通過優(yōu)化條件得到較高載藥量。其中,MIL-100(Fe)的最高載藥量為0.261 g/g載體;MOF-5的最高載藥量為0.296 g/g載體;ZIF-8的最高載藥量為0.505 g/g載體。對(duì)比載藥前后的MOF載體,結(jié)構(gòu)及穩(wěn)定性并未發(fā)生變化,說明藥物的填充并沒有改變MOF原有的結(jié)構(gòu)和性質(zhì)。采用動(dòng)態(tài)透析法進(jìn)行體外釋藥實(shí)驗(yàn),對(duì)三種MOF載體的體外釋藥進(jìn)行了研究。體外釋藥曲線有明顯的緩釋效果,表明其可在長時(shí)間內(nèi)持續(xù)釋放藥物,延長了作用時(shí)間也降低了給藥次數(shù)。證明以金屬有機(jī)骨架為載體負(fù)載5-Fu能提高5-Fu的抗腫瘤療效和病變部位的局部藥物濃度,可作為一種定位給藥制劑,降低了5-Fu的毒性的同時(shí)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.
【學(xué)位授予單位】：沈陽師范大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：O627;TQ460.1

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本文編號(hào)：1510517