Iron-based metal-organic frameworks (Fe-MOFs) have emerged as promising candidates for drug delivery applications due to their low toxicity, structural flexibility, and safe biodegradation in a physiological environment. Here, we studied two types of Fe-MOFs: MIL-53 and MIL-88B, for in vitro drug loading and releasing of ibuprofen as a model drug. Both Fe-MOFs are based on the same iron clusters and organic ligands but form different crystal structures as a result of two different nucleation pathways. The MIL-53 structure demonstrates one-dimensional channels, while MIL-88B exhibits a three-dimensional cage structure. Our studies show that MIL-53 adsorbs more ibuprofen (37.0 wt %) compared to MIL-88B (19.5 wt %). A controlled drug release was observed in both materials with a slower elution pattern in the case of the ibuprofen-encapsulated MIL-88B. This indicates that a complex cage structure of MIL-88 is beneficial to control the rate of drug release. A linear correlation was found between cumulative drug release and the degree of material degradation, suggesting the biodegradation of Fe-MILs as the main drug elution mechanism. The cytotoxicity of MIL-88B was evaluated in vitro with NIH-3T3 Swiss mouse fibroblasts, and it shows that MIL-88B has no adverse effects on cell viability up to 0.1 mg/mL. This low toxicity was attributed to the morphology of MIL-88B nanocrystals. The very low toxicity and controlled drug release behavior of Fe-MIL-88B suggest that better materials for drug-delivery applications can be created by controlling not only the composition but also the crystal structure and nanoparticle morphology of the material.
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