Performance of MIL-101(Cr) and MIL-101(Cr)-Pore Expanded as Drug Carriers for Ibuprofen and 5-Fluorouracil Delivery.

Metal-organic frameworks (MOFs) have been extensively investigated as nanocarriers for drug delivery applications owing to their remarkable surface area and porosity, which allow for impregnation of large quantities of drugs with fast pharmacokinetics. In this work, we developed a pore-expanded version of MIL-101(Cr), MIL-101(Cr)-P, and assessed its potential as a carrier for ibuprofen and 5-fluorouracil drugs along with its regular MIL-101(Cr) analogue. The pore expansion strategy gave rise to a higher surface area and mesopore volume for MIL-101(Cr)-P relative to regular MIL-101(Cr). The characterization results revealed successful incorporation of 30, 50, and 80 wt % of both drugs within the MOF structure. Upon incorporation of species, the surface area and porosity of the two MOF carriers decreased drastically; however, the drug-loaded MOFs still retained some degree of porosity, even at high drug loadings. For both drugs, the delivery experiments conducted in phosphate-buffered saline (PBS) showed that MIL-101(Cr)-P possessed better pharmacokinetic behavior than MIL-101(Cr) by delivering higher amounts of drug at all three loadings and exhibiting much faster release rates. Such behavior was originated from large mesopores that were created during pore expansion, providing diffusional pathways for efficient delivery of the drugs. The highest rate constant obtained by fitting the release kinetics to the Higuchi model was found to be 0.44 h-1/2 for the release of 30 wt % 5-fluorouracil from MIL-101(Cr)-P. The findings of this study highlight the role of tuning physiochemical properties of MOFs in improving their pharmacokinetic behavior as drug carriers.

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

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.