Synthesis, modification, characterization, and in vitro evaluation of chitosan-hyaluronic acid coated MIL-100 (Fe) nanoparticles for methotrexate delivery in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation of the joints, leading to pain, swelling, and potential joint destruction. Effective management of RA is crucial to improve patients' quality of life and prevent long-term disability. Methotrexate (MTX) is a widely used disease-modifying antirheumatic drug (DMARD) that has shown efficacy in treating RA. However, its use is often limited by significant adverse effects, particularly on healthy tissues and organs, including hepatotoxicity, myelosuppression, and gastrointestinal complications. Therefore, developing targeted drug delivery systems (DDSs) for MTX is essential to enhance its therapeutic effects while minimizing systemic toxicity. Metal-organic frameworks (MOFs), specifically MIL-100(Fe), present a promising approach for targeted drug delivery in RA treatment due to their high porosity, large surface area, and excellent loading capacity. The acid-responsive properties of MIL-100(Fe) make it particularly suitable for targeting the acidic microenvironment of inflamed joints. In this study, we synthesized MIL-100(Fe) using a microwave-assisted method and embedded MTX within these nanocarriers. The nanocarriers were subsequently coated with chitosan and modified with hyaluronic acid through 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC). Comprehensive characterization techniques such as dynamic light scattering (DLS), zeta potential analysis, Brunauer-Emmett-Teller (BET) surface area measurement, X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), and field emission scanning electron microscopy (FESEM) were employed to evaluate the nanoparticles. Additionally, we assessed cell cytotoxicity and cellular uptake in macrophage cell lines. Overall, the results indicate that the prepared MIL-100(Fe) nanoparticles are a suitable DDS for targeted MTX delivery in RA treatment.