Hyaluronic Acid–Targeted PLGA Nanoparticles for Methotrexate Delivery in Rheumatoid Arthritis
Autores/as
-
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/2026.03.02.2Palabras clave:
EnglishResumen
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.
Citas
1. Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. Lancet. 2016;388(10055):2023–2038. doi:10.1016/S0140-6736(16)30173-8
2. Firestein GS, McInnes IB. Immunopathogenesis of rheumatoid arthritis. Immunity. 2017;46(2):183–196. doi:10.1016/j.immuni.2017.02.006
3. Guo Q, Wang Y, Xu D, Nossent J, Pavlos NJ, Xu J. Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies. Bone Res. 2018;6:15. doi:10.1038/s41413-018-0016-9
4. Cronstein BN, Aune TM. Methotrexate and its mechanisms of action in inflammatory arthritis. Nat Rev Rheumatol. 2020;16(3):145–154. doi:10.1038/s41584-019-0352-4
5. Singh JA, Saag KG, Bridges SL Jr, et al. 2019 update of the American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care Res. 2019;71(6):684–699. doi:10.1002/acr.23780
6. Danhier F, Ansorena E, Silva JM, Coco R, Le Breton A, Préat V. PLGA-based nanoparticles: an overview of biomedical applications. J Control Release. 2012;161(2):505–522. doi:10.1016/j.jconrel.2012.01.043
7. Makadia HK, Siegel SJ. Poly(lactic-co-glycolic acid) (PLGA) is a biodegradable controlled drug delivery carrier. Polymers (Basel). 2011;3(3):1377–1397. doi:10.3390/polym3031377
8. Owens DE, Peppas NA. Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int J Pharm. 2006;307(1):93–102. doi:10.1016/j.ijpharm.2005.10.010
9. Zhu S, Zhang T, Jiang C, et al. CD44-targeted hyaluronic acid-modified nanoparticles for rheumatoid arthritis therapy. Biomater Sci. 2022;10(4):934–947. doi:10.1039/d1bm01538k
10. Park JS, Choi J, Kim Y, et al. Methotrexate-loaded nanoparticles ameliorate experimental rheumatoid arthritis with reduced systemic toxicity. Int J Nanomedicine. 2022;17:809–824. doi:10.2147/IJN.S338421
11. Alexis F, Pridgen E, Molnar LK, Farokhzad OC. Factors affecting the clearance and biodistribution of polymeric nanoparticles. Mol Pharm. 2008;5(4):505–515. doi:10.1021/mp800051m
12. Benne N, van Duijn J, Kuiper J, Jiskoot W, Slütter B. Nanoparticles for inducing antigen-specific T-cell tolerance. Front Immunol. 2022;13:827815. doi:10.3389/fimmu.2022.827815
13. Hunter Z, McCarthy DP, Yap WT, et al. A biodegradable nanoparticle platform for antigen-specific immune tolerance. ACS Nano. 2014;8(3):2148–2160. doi:10.1021/nn406032q
14. Ghorpade VS, Yadav AV, Dias RJ. Development of methotrexate-loaded polymeric nanoparticles using solvent displacement. Pharm Nanotechnol. 2021;9(3):195–204. doi:10.2174/2211738509666210229115950
15. Li Z, Hu Y, Fang J, et al. pH-responsive release of methotrexate from PLGA nanoparticles for inflammation-triggered therapy. Acta Biomater. 2023;159:254–266. doi:10.1016/j.actbio.2023.01.025
16. Mosmann T. Rapid colorimetric assay for cellular growth and survival. J Immunol Methods. 1983;65(1–2):55–63. doi:10.1016/0022-1759(83)90303-4
17. Chen Y, Zhang Y, Yin Q, et al. Methotrexate-loaded chitosan nanoparticles suppress inflammatory mediators in activated macrophages. Carbohydr Polym. 2020;236:116017. doi:10.1016/j.carbpol.2020.116017
18. Zhang Q, Honko AN, Zhou J, et al. Nanoparticle modulation of macrophage polarization in autoimmune and inflammatory diseases. Nano Today. 2023;52:102021. doi:10.1016/j.nantod.2023.102021
19. Walvekar P, Ghadge SK, Patil S, et al. Hyaluronic acid-based nanocarriers for arthritis: current status and future perspectives. Int J Biol Macromol. 2023;235:123878. doi:10.1016/j.ijbiomac.2023.123878
20. Jaaffer MD, Abdulhussein EI, Abbas AW, Chaloop AM. Silicon dioxide nanoparticles enhance rice blast resistance in Oryza sativa. Agric Biotechnol J. 2026;18(1):339–362.
21. Brand DD, Latham KA, Rosloniec EF. Collagen-induced arthritis. Nat Protoc. 2007;2(5):1269–1275. doi:10.1038/nprot.2007.174
22. Beg S, Rahman M, Jain A, Saini S, Hasnain MS, Swain S. Nanoparticles for targeted drug delivery to rheumatoid arthritis: a comprehensive review. J Control Release. 2021;333:97–126. doi:10.1016/j.jconrel.2020.12.043
23. Li X, Hou Y, Zhang P, et al. pH-sensitive polymeric carriers for controlled drug delivery. J Mater Chem B. 2020;8:10072–10090. doi:10.1039/d0tb00992b
24. Niu J, Li Z, Yuan J, et al. pH-responsive nanocarriers for rheumatoid arthritis microenvironment. Adv Ther. 2022;5(2):2200014. doi:10.1002/adtp.202200014
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Derechos de autor 2026 Marwa D. Jaaffer, Sheimaa J. Hadi, Ammar M. Chaloop (Author)
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