Department of Chemical & Biochemical Engineering, Missouri University of Science and Technology, Rolla, Missouri 65409-1230, United States.
ACS Appl Bio Mater. 2021 Apr 19;4(4):3423-3432. doi: 10.1021/acsabm.1c00009. Epub 2021 Mar 12.
Metal-organic frameworks (MOFs) have gained considerable attention as drug delivery platforms over the past decade owing to their tunable physiochemical properties, biodiversity, and capability to encapsulate sizable active compound loadings. Nevertheless, many fundamental properties pertaining to MOFs' pharmacokinetic performances as drug carriers have been poorly investigated. One such property is the relationship between the MOF metal center solubility and drug release rate. In this study, we investigated this relationship within the M-MOF-74 family by impregnating 30 or 50 wt % curcumin on either Mg-, Ni-, Zn-, or Co-MOF-74. The drug delivery performance of the materials was assessed in phosphate buffered saline solution by high-performance liquid chromatography over a time period of 0-24 h. From these experiments, it was determined that the 30 wt % curcumin loading led to increased drug delivery and kinetics compared to the 50 wt % loading regardless of the metal center, as the lower drug concentration did not hinder diffusion from the MOF pores. As such, the optimal curcumin loading within the M-MOF-74 family was concluded to be greater than 30 wt % but less than 50 wt %. These experiments also revealed that using Mg-MOF-74 as a drug carrier produced a twofold enhancement in the release rate from 0.15 to 0.30 h compared to the other three metal centers, where Mg-MOF-74's improved pharmacokinetics were attributed to the increased group II Mg solubility compared to Ni, Co, or Zn transition metals. On the basis of these findings, it was concluded that to promote rapid pharmacokinetics, it is essential to use MOFs with more soluble metal centers to promote dissolution of the nanocarrier. While this study focused on M-MOF-74, we expect that this conclusion has implications to other crystallites as well.
金属有机骨架(MOFs)由于其可调节的物理化学性质、生物多样性以及封装大量活性化合物负载的能力,在过去十年中作为药物传递平台引起了相当大的关注。然而,许多与 MOFs 作为药物载体的药代动力学性能相关的基本性质尚未得到充分研究。其中一个性质是 MOF 金属中心溶解度与药物释放速率之间的关系。在这项研究中,我们通过在 Mg-MOF-74、Ni-MOF-74、Zn-MOF-74 或 Co-MOF-74 上浸渍 30 或 50wt%的姜黄素来研究 M-MOF-74 家族中的这种关系。通过在 0-24 小时内用高效液相色谱法在磷酸盐缓冲盐溶液中评估材料的药物传递性能。从这些实验中可以确定,与 50wt%的负载相比,30wt%的姜黄素负载导致药物传递和动力学增加,而与金属中心无关,因为较低的药物浓度不会阻碍 MOF 孔内的扩散。因此,M-MOF-74 家族中最佳的姜黄素负载量被认为大于 30wt%但小于 50wt%。这些实验还表明,与其他三种金属中心相比,使用 Mg-MOF-74 作为药物载体可将释放速率从 0.15 小时提高到 0.30 小时,提高了两倍,其中 Mg-MOF-74 的改善药代动力学特性归因于与 Ni、Co 或 Zn 过渡金属相比,Mg 溶解度增加。基于这些发现,可以得出结论,为了促进快速药代动力学,必须使用具有更可溶的金属中心的 MOFs 来促进纳米载体的溶解。虽然这项研究集中在 M-MOF-74 上,但我们预计这一结论也适用于其他晶体。