Tailoring the structure of MIL-101(Fe) for co-delivery of anti-inflammatory therapeutic agents

Treating inflammation often requires the combined use of multiple agents due to the complexity of biological pathways. Metal-organic frameworks (MOFs), with adjustable structures and high loading capacities, offer a promising route for dual-drug delivery. However, designing MOF-based systems that can simultaneously incorporate and release two distinct anti-inflammatory compounds remains a challenge. In this study, MIL-101(Fe) materials were synthesized under varying temperatures and solvent volumes to tailor their physicochemical properties. Higher synthesis temperatures promoted the formation of more crystalline, microporous structures with well-defined octahedral particles, whereas lower temperatures favored defect-rich, less ordered frameworks. These structural features governed adsorption and enabled controlled release of naproxen sodium and curcumin, selected for complementary action mechanisms. Material synthesized at 110 °C with doubled solvent volumes displayed the most favorable porosity, V_micro/V_total = 0.5, and uniform morphology, achieving high co-adsorption capacity (468 mg/g for naproxen sodium, 160 mg/g for curcumin) along with sustained release (92% and 60% within 24 h at pH 6.8, respectively). Biological evaluation demonstrated that all systems suppressed the synthesis of inflammatory markers, including prostaglandins and IL-6. Notably, the hierarchically porous MIL-101(Fe) synthesized at 110 °C with a higher solvent volume exhibited the strongest COX-1 inhibition (38%), whereas the predominantly mesoporous sample obtained at 110 °C with the standard solvent volume showed greater COX-2 suppression (53%). Low cytotoxicity was observed at 200 μg/mL of the therapeutic agents-loaded carriers, with cell viability remaining over 90%. These findings highlight the potential of MIL-101(Fe) as a tunable carrier for synergistic anti-inflammatory substance delivery.