Drug Delivery on Mg-MOF-74: The Effect of Drug Solubility on Pharmacokinetics

药代动力学 溶解度 药物输送 化学 药品 药理学 有机化学 医学
作者
Neila Pederneira,Kyle Newport,Shane Lawson,Ali A. Rownaghi,Fateme Rezaei
出处
期刊:ACS applied bio materials [American Chemical Society]
卷期号:6 (6): 2477-2486 被引量:23
标识
DOI:10.1021/acsabm.3c00275
摘要

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), N2 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.
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