Linda and Bipin Doshi Department of Chemical and Biochemical Engineering, Missouri University of Science and Technology, Rolla, Missouri 65409-1230, United States.
Department of Chemistry, Cleveland State University, 2121 Euclid Avenue, Cleveland, Ohio 44115, United States.
ACS Appl Bio Mater. 2023 Jun 19;6(6):2477-2486. doi: 10.1021/acsabm.3c00275. Epub 2023 Jun 8.
Biocompatible metal-organic frameworks (MOFs) have emerged as potential nanocarriers for drug delivery applications owing to their tunable physiochemical properties. Specifically, Mg-MOF-74 with soluble metal centers has been shown to promote rapid pharmacokinetics for some drugs. In this work, we studied how the solubility of drug impacts the pharmacokinetic release rate and delivery efficiency by impregnating various amounts of ibuprofen, 5-fluorouracil, and curcumin onto Mg-MOF-74. The characterization of the drug-loaded samples via X-ray diffraction (XRD), N physisorption, and Fourier transform infrared (FTIR) confirmed the successful encapsulation of 30, 50, and 80 wt % of the three drugs within the MOF structure. Assessment of the drug delivery performances of the MOF under its various loadings via HPLC tests revealed that the release rate is a direct function of drug solubility and molecular size. Of the three drugs considered under fixed loading condition, the 5-fluorouracil-loaded MOF samples exhibited the highest release rate constants which was attributed to the highest degree of solubility and smallest molecular size of 5-fluorouracil relative to ibuprofen and curcumin. It was also noted that the release kinetics decreases with drug loading, due to a pharmacokinetic shift in release mechanism from singular to binary modes of compound diffusion. The findings of this study highlight the effects of drug's physical and chemical properties on the pharmacokinetic rates from MOF nanocarriers.
生物相容的金属有机骨架(MOFs)由于其可调节的物理化学性质,已成为药物传递应用的潜在纳米载体。具体来说,具有可溶性金属中心的 Mg-MOF-74 已被证明可以促进某些药物的快速药代动力学。在这项工作中,我们研究了药物的溶解度如何通过浸渍不同量的布洛芬、5-氟尿嘧啶和姜黄素到 Mg-MOF-74 上来影响药代动力学释放率和传递效率。通过 X 射线衍射(XRD)、N 物理吸附和傅里叶变换红外(FTIR)对载药样品进行的表征证实了三种药物中的 30、50 和 80wt%成功封装在 MOF 结构内。通过 HPLC 测试评估 MOF 在其各种负载下的药物传递性能表明,释放速率是药物溶解度和分子大小的直接函数。在固定负载条件下考虑的三种药物中,负载 5-氟尿嘧啶的 MOF 样品表现出最高的释放速率常数,这归因于 5-氟尿嘧啶相对于布洛芬和姜黄素具有最高的溶解度和最小的分子大小。还注意到,由于释放机制从单一模式到化合物扩散的二元模式的药代动力学转变,释放动力学随药物负载的增加而降低。这项研究的结果强调了药物物理和化学性质对从 MOF 纳米载体中获得的药代动力学速率的影响。