Hyaluronate-functionalized hydroxyapatite nanoparticles laden with methotrexate and teriflunomide for the treatment of rheumatoid arthritis

Rheumatoid arthritis (RA), an autoimmune inflammatory disorder is currently incurable. Methotrexate and Teriflunomide are routinely prescribed drugs but their uses are limited due to severe hepatotoxicity. Hyaluronic acid (HYA) is a targeting ligand for CD44 receptors overexpressed on inflamed macrophages. The present investigation aimed at design and fabrication of HYA coated hydroxyapatite nanoparticles (HA-NPs) loaded with Methotrexate (MTX) and Teriflunomide (TEF) (HAMT-NPs) to form HYA-HAMT-NPs for the treatment of RA. HYA-HAMT-NPs showed the nanoscale size of 274.9 +/- 64 nm along with a zeta potential value of -26.80 +/- 6.08 mV. FTIR spectra of HYA and HYA-HAMT-NPs proved the coating of HYA on HYA-HAMT-NPs. HYA-HAMT-NPs showed less cell viability compared to drugs on RAW 264.7 macrophage cells. A biodistribution study by gamma scintigraphy imaging further strengthened the results by revealing significantly higher (p<0.05) percentage radioactivity (76.76%) of HYA-HAMT-NPs in the synovial region. The results obtained by pharmacodynamic studies ensured the better efficacy of HYA-HAMT-NPs in preventing disease progression and promoting articular regeneration. Under hepatotoxicity evaluation, liver histopathology and liver enzyme assay revealed similar to 29% hepatotoxicity was reduced by HYA-HAMT-NPs when compared to conventional FOLITRAX-10 and AUBAGIO oral treatments. Overall, the results suggest that HYA- HAMT-NP is a promising delivery system to avoid drug-induced hepatotoxicity in RA. (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

HYA-HAMT-NP is a promising delivery system to avoid drug-induced hepatotoxicity in RA, showing better efficacy in treating RA.