Hyaluronic Acid–Targeted PLGA Nanoparticles for Methotrexate Delivery in Rheumatoid Arthritis
Authors
-
Marwa D. Jaaffer
Department of Environmental Health, College of Energy & Environmental Sciences, Al-Karkh University of Science, Baghdad, Iraq
https://orcid.org/0009-0007-3855-1819
- Sheimaa J. Hadi Department of Environmental Health, College of Energy and Environmental Sciences, Al-Karkh University of Science, Baghdad, Iraq.
- Ammar M. Chaloop Department of Environmental Health, College of Energy & Environmental Sciences, Al-Karkh University of Science, Baghdad, Iraq
DOI:
https://doi.org/10.70099/BJ/2026.03.02.2Keywords:
Rheumatoid arthritis, Methotrexate, Hyaluronic acid, PLGA–PEG nanoparticles, Targeted drug delivery, CD44 receptorAbstract
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation and eventual joint damage. Despite the standard use of methotrexate (MTX) as the first-line treatment, it has low plasma half-life, tissue selectivity, and toxicity, which limits its clinical effectiveness. This paper has developed hyaluronic acid-functionalized PLGA-PEG nanoparticles (HA-PLGA-PEG/MTX NPs) to enhance targeting of inflamed joints via CD44. The nanoparticles were synthesized using a modified nanoprecipitation method, followed by characterization by DLS, TEM, FTIR, and an in vitro release assay. The refined formula exhibited a mean particle size of about 165 nm, a small polydispersity index, and a negative zeta potential, and FTIR confirmed the successful conjugation of HA. There was a long-term release profile of MTX (72 hours). HA-decorated nanoparticles exhibited significantly greater cellular uptake in MH7A synoviocytes and in RAW 264.7 macrophages than non-targeted NPs and more potent inhibition of LPS-triggered nitric oxide, TNF-α and IL-6 (p < 0.05). In vivo testing in the collagen-induced arthritis (CIA) rat model showed that HA-PLGA-PEG/MTX NPs had better therapeutic effects, including reduced paw swelling, restoration of normal joint histology, and reduced clinical arthritis grade, compared with free MTX. HA-PLGA-PEG/MTX NPs exhibited much better anti-inflammatory properties due to targeted delivery, sustained release, and increased intracellular accumulation. The results of the study demonstrate the promising nature of this nanocarrier system to augment MTX treatment in RA and other autoimmune inflammatory diseases.
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