Construction and Evaluation of pH-Responsive Nitrogen-Containing Metal–Organic Frameworks as Oral Drug Carriers
Metal–organic framework (MOF) is a porous material composed of metal ions/clusters and organic ligands. It has attracted much attention due to its high specific surface area, good biocompatibility, chemical modifiability, and diversity of components. Among many MOFs, zirconium-based MOFs are particularly suitable for biological applications due to their optimal stability and low toxicity to hydrolysis. However, due to the weak coordination bonds between many metal clusters and organic ligands, most MOFs are prone to collapse in acidic environments, and the stability of MOFs as drug carriers cannot be guaranteed so that they cannot be widely used as oral drug carriers. This study synthesized the three MOFs using metal Zr ion clusters as the center and different nitrogen-containing organic ligands, which are stable in gastric acid, namely, UiO-66-PDC, UiO-66-NH 2 , and UiO-66-NO 2 . The anionic drug loxoprofen (LOX) was loaded and characterized using scanning electron microscopy, infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry, and x-ray diffraction. The adsorption and release behaviors of LOX and the three MOFs were studied from the molecular point of view by computer simulation. A series of behaviors and mechanisms of pH-responsive nitrogen-containing MOFs as oral drug carriers were further explored through rat pharmacokinetic experiments, the everted gut sac experiments, and intestinal absorption mechanism experiments. The experimental results show that there is a strong electrostatic interaction between anionic drug LOX and UiO-66-PDC under simulated gastric acid environment, which prolongs the half-life of the drug, proving that LOX@UiO-66-PDC is a promising new oral drug delivery system.
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