Abstract：
The toxicity for the human body of non-steroidal anti-inflammatory drugs (NSAIDs) overdoses is a consequence of their low water solubility, high doses, and facile accessibility to the population. New drug delivery systems (DDS) are necessary to overcome the bioavailability and toxicity related to NSAIDs. In this context, UiO-66(Zr) metal-organic framework (MOF) shows high porosity, stability, and load capacity, thus being a promising DDS. However, the adsorption and release capability for different NSAIDs is scarcely described. In this work, the biocompatible UiO-66(Zr) MOF was used to study the adsorption and release conditions of ibuprofen, naproxen, and diclofenac using a theoretical and experimental approximation. DFT results showed that the MOF-drug interaction was due to an intermolecular hydrogen bond between protons of the groups in the defect sites, (μ3 - OH, and - OH2) and a lone pair of oxygen carboxyl functional group of the NSAIDs. Also, the experimental results suggest that the solvent where the drug is dissolved affects the adsorption process. The adsorption kinetics are similar between the drugs, but the maximum load capacity differs for each drug. The release kinetics assay showed a solvent dependence kinetics whose maximum liberation capacity is affected by the interaction between the drug and the material. Finally, the biological assays show that none of the systems studied are cytotoxic for HMVEC. Additionally, the wound healing assay suggests that the UiO-66(Zr) material has potential application on the wound healing process. However, further studies should be done.
摘要：
非甾体抗炎药（NSAIDs）过量对人体的毒性是其水溶性低的结果，高剂量,和人口容易进入。新的药物递送系统(DDS)对于克服与NSAID相关的生物利用度和毒性是必要的。在这种情况下，UiO-66(Zr)金属有机骨架(MOF)显示出高孔隙率,稳定性,和负载能力，因此是一个有前途的DDS。然而,几乎没有描述不同NSAIDs的吸附和释放能力。在这项工作中,生物相容性UiO-66（Zr）MOF用于研究布洛芬的吸附和释放条件，萘普生,和双氯芬酸使用理论和实验近似。DFT结果表明，MOF-药物相互作用是由于缺陷位点基团的质子之间的分子间氢键，(μ3-OH,和-OH2）和NSAID的一对孤对氧羧基官能团。此外，实验结果表明，溶解药物的溶剂会影响吸附过程。药物之间的吸附动力学相似，但每种药物的最大负载能力不同。释放动力学分析显示出溶剂依赖性动力学，其最大释放能力受药物与材料之间相互作用的影响。最后,生物试验表明,所研究的系统中没有一个对HMVEC具有细胞毒性。此外,伤口愈合试验表明UiO-66(Zr)材料在伤口愈合过程中具有潜在的应用。然而,应该做进一步的研究。
