多孔芳香骨架材料PAF-1修饰吸附活性位点对于药物缓释的影响

Effects of activated sites in porous aromatic frameworks PAF-1 for drug loading and release

近年来,多孔芳香骨架材料由于其较高的比表面积、较大的孔容、良好的热和化学稳定性而在气体吸附与分离、光电和催化等方面有了极大的发展。同时,芳香骨架的可修饰性使得在其孔道中修饰不同的官能团以进行不同的应用成为可能。其中一个重要的应用就是利用多孔芳香骨架材料作为药物缓释应用的合适候选材料。本文通过镍(0)催化的Yamamoto-type Ullmann偶联反应合成多孔芳香骨架材料PAF-1,通过硝化还原反应引入具有吸附活性的氨基官能团,并精确调控多孔材料的氨基含量,研究吸附活性位点对布洛芬药物分子的相互作用及影响PAF-1-NH_2药物缓释效果的因素。结果发现,PAF-1中的氨基含量与载药率变化呈正相关,而材料的比表面积与载药率呈现负相关关系。由此说明,PAF-1孔道结构中修饰的活性位点的数目对载药率的影响是主要的。氨基含量最高的PAF-1-NH_2-48 h具有1.203 g·g^(-1)的载药量,高于目前报道的其他有机多孔材料对布洛芬的载药率。药物缓释实验证明,吸附活性位点数目的增多导致药物释放率逐渐增大,PAF-1-NH_2-48 h的药物缓释效果最好,10 h后达到最大药物释放量0.83 g·g^(-1)。

In recent years, porous aromatic frameworks (PAFs) have made great progress for gas adsorption and separation, sensing and catalysis applications, thanks to their high specific surface area, tailorable structures and good thermal and chemical stability. Moreover, the aromatic building units provide the possibility of modifying the skeleton with diverse functional groups that possess various applications, such as using PAF as a candidate for drug loading and release. Herein, the porous aromatic framework PAF-1 was synthesized by the Yamamoto type Ullmann coupling reaction catalyzed by nickel (0). The nitrification degree was carefully controlled to give PAF-1-NH2 with different amino content in the pore structure. The amino group was used as the active site, and ibuprofen was used as a targetting drug model. The interaction between the amino group of the active site and the ibuprofen molecule was studied, as well as the factors affecting the sustained release of PAF-1-NH2 . It is found that when the amounts of modified amino groups in the pore structure of PAF-1 increases, the specific surface area of PAF-1-NH2 decreases gradually, with the increasing drug loading amounts. This indicates that the number of modified active sites in the PAF-1 porous structure has the predominate effect on the drug loading rate. Among them, PAF-1-NH2-48 h with the highest amino content has a drug loading of 1.203 g·g^-1 , which is the highest drug loading rate of ibuprofen by organic porous materials. The drug release experiment proves that with the increase of the number of amino groups, the drug release rate gradually increases, and the drug release of PAF-1-NH2-48 h obtained after 48 hours of nitrification is as high as 0.83 g·g^-1 .