多孔材料ZIF-8的制备及其对布洛芬的载药性能

Preparation of the porous ZIF-8 and the behaviors of loading ibuprofen

  • 摘要: 难溶性药物的低溶解度,严重限制了其口服生物利用度。对此,结合金属-有机框架(MOFs)材料具有疏水性和高比表面积的特点,以溶液共沉淀法制备了MOF多孔材料ZIF-8作为载药基底。通过改变Zn2+与2-甲基咪唑(2-methylimidazole)的摩尔比,进而对ZIF-8的比表面积及孔径分布进行调控,然后对难溶性药物布洛芬(IBP)的负载性能进行研究。研究结果表明:当Zn2+与2-甲基咪唑的摩尔比为1∶8时,材料ZIF-8(8)具有最大的比表面积和孔体积,分别为1187 m2/g和1.183 cm3/g,其对难溶性药物布洛芬的负载量高达21.8%。且药物载体复合材料IBP-ZIF-8(8)表现出良好的体外溶出度,在pH为2.5和7.4的磷酸缓冲溶液中,其累积溶出度均为98%左右。ZIF-8(8)处理的小鼠单核巨噬细胞白血病细胞(Mouse mononuclear macrophages cells,RAW246.7)存活率均高达94%以上,表现出良好的生物安全性。

     

    Abstract: Oral bioavailability of poorly soluble drugs is severely limited due to their low solubility. In recent years, metal-organic frameworks (MOFs) materials have attracted much attention because of their hydrophobicity and high specific surface area. In this paper, the porous ZIF-8, one of MOF family materials, were prepared by solution co-precipitation method. The specific surface area and pore size distribution of ZIF-8 were optimized by changing the molar ratio of Zn2+ to 2-methylimidazole. In addition, ZIF-8 were used as the carrier for ibuprofen (IBP), a poorly soluble drug, and its loading performance was studied in detail. The results showed that when the molar ratio of Zn2+ to 2-methylimidazole was 1∶8, ZIF-8(8) had the largest specific surface area (1187 m2/g) and pore volume (1.183 cm3/g). And the loading capacity of ZIF-8(8) on IBP was as high as 21.8%. The drug carrier composite (IBP-ZIF-8(8)) showed a well dissolution rate in vitro, and its cumulative dissolution rate was about 98% in phosphate buffer solution with pH of 2.5 and 7.4. The survival rate of RAW246.7 cells treated with IBP-ZIF-8(8) was over 94%, demonstrating satisfied biosafety. ZIF-8(8) with excellent specific surface area, pore volume, good loaded-IBP performance and biosafety has great potential applications in drug controlled-release system.

     

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