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image of Mesoporous Silica Nanoparticles with Dual Function of Anti-Inflammatory and Lubrication for Rheumatoid Arthritis Treatment

Abstract

Introduction

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease leading to cartilage degeneration and destruction. Friction between articular cartilage surfaces exacerbates these effects. Currently, clinical therapy is dominated by single anti-inflammatory or lubrication treatments. Preparations with both anti-inflammatory and lubrication effects are of great significance for RA treatment. In this study, a mesoporous silica nanosystem (MSN@DCF-HA) with dual functions of anti-inflammation and joint lubrication was developed for RA therapy.

Methods

Mesoporous silica nanoparticles (MSN) were prepared by the template method. MSN@DCF-HA was synthesized by encapsulating diclofenac (DCF) into MSN and then coating it with hyaluronic acid (HA). Drug loading capacity, encapsulation efficiency, release, and biosafety of MSN@DCF-HA were evaluated. An RA rat inflammation model was used to assess therapeutic efficacy.

Results

TEM revealed that MSN@DCF-HA was spherical and size-uniform. Experiments demonstrated favorable biocompatibility and stability. The system facilitated sustained DCF release in acidic PBS. results showed significant reduction in paw swelling, inflammatory factors, and bone damage in the MSN@DCF-HA group. Cell toxicity experiments, hemolysis experiments, and experiments indicated that it has no significant toxicity.

Discussion

MSN@DCF-HA, by loading DCF to exert anti-inflammatory effects and HA to provide external lubrication, joint protection, and synergistic treatment of RA, has demonstrated excellent therapeutic effects, providing a new strategy for RA treatment.

Conclusion

MSN@DCF-HA was successfully prepared, exhibited slow drug release in acidic environments, and its anti-inflammation and joint lubrication exerted synergistic effects on RA rats without obvious toxicity. This work proposes a novel therapeutic strategy for rheumatoid arthritis.

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2026-01-13
2026-02-20

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References

  1. Fearon U. Hanlon M.M. Floudas A. Veale D.J. Cellular metabolic adaptations in rheumatoid arthritis and their therapeutic implications. Nat. Rev. Rheumatol. 2022 18 7 398 414 10.1038/s41584‑022‑00771‑x 35440762
    [Google Scholar]
  2. Langley P.C. Mu R. Wu M. Dong P. Tang B. The impact of rheumatoid arthritis on the burden of disease in urban China. J. Med. Econ. 2011 14 6 709 719 10.3111/13696998.2011.611201 21899486
    [Google Scholar]
  3. Myasoedova E. Davis J. Matteson E.L. Crowson C.S. Is the epidemiology of rheumatoid arthritis changing? Results from a population-based incidence study, 1985–2014. Ann. Rheum. Dis. 2020 79 4 440 444 10.1136/annrheumdis‑2019‑216694 32066556
    [Google Scholar]
  4. Di Matteo A. Bathon J.M. Emery P. Rheumatoid arthritis. Lancet 2023 402 10416 2019 2033 10.1016/S0140‑6736(23)01525‑8 38240831
    [Google Scholar]
  5. Gravallese E.M. Firestein G.S. Rheumatoid arthritis — Common origins, divergent mechanisms. N. Engl. J. Med. 2023 388 6 529 542 10.1056/NEJMra2103726 36780677
    [Google Scholar]
  6. Shrivastava A.K. Pandey A. Inflammation and rheumatoid arthritis. J. Physiol. Biochem. 2013 69 2 335 347 10.1007/s13105‑012‑0216‑5 23385669
    [Google Scholar]
  7. Guo Q. Wang Y. Xu D. Nossent J. Pavlos N.J. Xu J. Rheumatoid arthritis: Pathological mechanisms and modern pharmacologic therapies. Bone Res. 2018 6 1 15 10.1038/s41413‑018‑0016‑9 29736302
    [Google Scholar]
  8. Bao J. Chen W. Wu L. Lubricin: A novel potential biotherapeutic approaches for the treatment of osteoarthritis. Mol. Biol. Rep. 2011 38 5 2879 2885 10.1007/s11033‑010‑9949‑9 20099082
    [Google Scholar]
  9. Le H. Xu W. Zhuang X. Chang F. Wang Y. Ding J. Mesenchymal stem cells for cartilage regeneration. J. Tissue Eng. 2020 11 2041731420943839 10.1177/2041731420943839 32922718
    [Google Scholar]
  10. Smith M.H. Berman J.R. What is rheumatoid arthritis? JAMA 2022 327 12 1194 10.1001/jama.2022.0786 35315883
    [Google Scholar]
  11. Konzett V. Aletaha D. Management strategies in rheumatoid arthritis. Nat. Rev. Rheumatol. 2024 20 12 760 769 10.1038/s41584‑024‑01169‑7 39448800
    [Google Scholar]
  12. Brown P. Pratt A.G. Hyrich K.L. Therapeutic advances in rheumatoid arthritis. BMJ 2024 384 e070856 10.1136/bmj‑2022‑070856 38233032
    [Google Scholar]
  13. Seror J. Merkher Y. Kampf N. Collinson L. Day A.J. Maroudas A. Klein J. Articular cartilage proteoglycans as boundary lubricants: structure and frictional interaction of surface-attached hyaluronan and hyaluronan--aggrecan complexes. Biomacromolecules 2011 12 10 3432 3443 10.1021/bm2004912 21823600
    [Google Scholar]
  14. Hu Q. Zhang F. Wei Y. Liu J. Nie Y. Xie J. Yang L. Luo R. Shen B. Wang Y. Drug-embedded nanovesicles assembled from peptide-decorated hyaluronic acid for rheumatoid arthritis synergistic therapy. Biomacromolecules 2023 24 8 3532 3544 10.1021/acs.biomac.3c00294 37417966
    [Google Scholar]
  15. Chatzidionysiou K. Emamikia S. Nam J. Ramiro S. Smolen J. van der Heijde D. Dougados M. Bijlsma J. Burmester G. Scholte M. van Vollenhoven R. Landewé R. Efficacy of glucocorticoids, conventional and targeted synthetic disease-modifying antirheumatic drugs: a systematic literature review informing the 2016 update of the EULAR recommendations for the management of rheumatoid arthritis. Ann. Rheum. Dis. 2017 76 6 1102 1107 10.1136/annrheumdis‑2016‑210711 28356243
    [Google Scholar]
  16. Cooper C. Chapurlat R. Al-Daghri N. Herrero-Beaumont G. Bruyère O. Rannou F. Roth R. Uebelhart D. Reginster J.Y. Safety of Oral non-selective non-steroidal anti-inflammatory drugs in osteoarthritis: what does the literature say? Drugs Aging 2019 36 S1 15 24 (Suppl. 1) 10.1007/s40266‑019‑00660‑1 31073921
    [Google Scholar]
  17. Bruno M.C. Cristiano M.C. Celia C. d’Avanzo N. Mancuso A. Paolino D. Wolfram J. Fresta M. Injectable drug delivery systems for osteoarthritis and rheumatoid arthritis. ACS Nano 2022 16 12 19665 19690 10.1021/acsnano.2c06393 36512378
    [Google Scholar]
  18. Janakiraman K. Krishnaswami V. Rajendran V. Natesan S. Kandasamy R. Novel nano therapeutic materials for the effective treatment of rheumatoid arthritis-recent insights. Mater. Today Commun. 2018 17 200 213 10.1016/j.mtcomm.2018.09.011 32289062
    [Google Scholar]
  19. Cheng W. Nie J. Xu L. Liang C. Peng Y. Liu G. Wang T. Mei L. Huang L. Zeng X. pH-sensitive delivery vehicle based on folic acid-conjugated polydopamine-modified mesoporous silica nanoparticles for targeted cancer therapy. ACS Appl. Mater. Interfaces 2017 9 22 18462 18473 10.1021/acsami.7b02457 28497681
    [Google Scholar]
  20. Xue Y. Niu W. Wang M. Chen M. Guo Y. Lei B. Correction to “engineering a biodegradable multifunctional antibacterial bioactive nanosystem for enhancing tumor photothermo-chemotherapy and bone regeneration”. ACS Nano 2021 15 9 15395 15396 10.1021/acsnano.1c06645 34468126
    [Google Scholar]
  21. Fallacara A. Baldini E. Manfredini S. Vertuani S. Hyaluronic acid in the third millennium. Polymers 2018 10 7 701 10.3390/polym10070701 30960626
    [Google Scholar]
  22. Hussain S. Ur-Rehman M. Arif A. Cailleau C. Gillet C. Saleem R. Noor H. Naqvi F. Jabeen A. Atta-ur-Rahman; Iqbal Choudhary, M.; Fattal, E.; Tsapis, N. Diclofenac prodrugs nanoparticles: An alternative and efficient treatment for rheumatoid arthritis? Int. J. Pharm. 2023 643 123227 10.1016/j.ijpharm.2023.123227 37453671
    [Google Scholar]
  23. Litwiniuk M. Krejner A. Speyrer M.S. Gauto A.R. Grzela T. Hyaluronic acid in inflammation and tissue regeneration. Wounds 2016 28 3 78 88 [PMID: 26978861
    [Google Scholar]
  24. Chen L.H. Xue J.F. Zheng Z.Y. Shuhaidi M. Thu H.E. Hussain Z. Hyaluronic acid, an efficient biomacromolecule for treatment of inflammatory skin and joint diseases: A review of recent developments and critical appraisal of preclinical and clinical investigations. Int. J. Biol. Macromol. 2018 116 572 584 10.1016/j.ijbiomac.2018.05.068 29772338
    [Google Scholar]
  25. Morgese G. Benetti E.M. Zenobi-Wong M. Molecularly engineered biolubricants for articular cartilage. Adv. Healthc. Mater. 2018 7 16 1701463 10.1002/adhm.201701463 29717824
    [Google Scholar]
  26. Wang P. Zhang Y. Lei H. Yu J. Zhou Q. Shi X. Zhu Y. Zhang D. Zhang P. Wang K. Dong K. Xing J. Dong Y. Hyaluronic acid-based M1 macrophage targeting and environmental responsive drug releasing nanoparticle for enhanced treatment of rheumatoid arthritis. Carbohydr. Polym. 2023 316 121018 10.1016/j.carbpol.2023.121018 37321721
    [Google Scholar]
  27. Vedadghavami A. He T. Zhang C. Amiji S.M. Hakim B. Bajpayee A.G. Charge-based drug delivery to cartilage: Hydrophobic and not electrostatic interactions are the dominant cause of competitive binding of cationic carriers in synovial fluid. Acta Biomater. 2022 151 278 289 10.1016/j.actbio.2022.08.010 35963518
    [Google Scholar]
  28. Li Y. Wang X. Gao Y. Zhang Z. Liu T. Zhang Z. Wang Y. Chang F. Yang M. Hyaluronic acid-coated polypeptide nanogel enhances specific distribution and therapy of tacrolimus in rheumatoid arthritis. J. Nanobiotechnology 2024 22 1 547 10.1186/s12951‑024‑02784‑y 39238027
    [Google Scholar]
  29. Marinho A. Nunes C. Reis S. Hyaluronic acid: A key ingredient in the therapy of inflammation. Biomolecules 2021 11 10 1518 10.3390/biom11101518 34680150
    [Google Scholar]
  30. Lei C. Liu X.R. Chen Q.B. Li Y. Zhou J.L. Zhou L.Y. Zou T. Hyaluronic acid and albumin based nanoparticles for drug delivery. J. Control. Release 2021 331 416 433 10.1016/j.jconrel.2021.01.033
    [Google Scholar]
  31. Kang L.J. Yoon J. Rho J.G. Han H.S. Lee S. Oh Y.S. Kim H. Kim E. Kim S.J. Lim Y.T. Park J.H. Song W.K. Yang S. Kim W. Self-assembled hyaluronic acid nanoparticles for osteoarthritis treatment. Biomaterials 2021 275 120967 10.1016/j.biomaterials.2021.120967 34153786
    [Google Scholar]
  32. Gorantla S. Gorantla G. Saha R.N. Singhvi G. CD44 receptor-targeted novel drug delivery strategies for rheumatoid arthritis therapy. Expert Opin. Drug Deliv. 2021 18 11 1553 1557 10.1080/17425247.2021.1950686 34190674
    [Google Scholar]
  33. Teriete P. Banerji S. Noble M. Blundell C.D. Wright A.J. Pickford A.R. Lowe E. Mahoney D.J. Tammi M.I. Kahmann J.D. Campbell I.D. Day A.J. Jackson D.G. Structure of the regulatory hyaluronan binding domain in the inflammatory leukocyte homing receptor CD44. Mol. Cell 2004 13 4 483 496 10.1016/S1097‑2765(04)00080‑2 14992719
    [Google Scholar]
  34. Chen C. Tang W. Jiang D. Yang G. Wang X. Zhou L. Zhang W. Wang P. Hyaluronic acid conjugated polydopamine functionalized mesoporous silica nanoparticles for synergistic targeted chemo-photothermal therapy. Nanoscale 2019 11 22 11012 11024 10.1039/C9NR01385G 31140527
    [Google Scholar]
  35. Wu Y. Chen W. Zeng Y. Ji Q. Yang Y. Guo X. Wang X. Inflammation-responsive mesoporous silica nanoparticles with synergistic anti-inflammatory and joint protection effects for rheumatoid arthritis treatment. Pharm. Res. 2024 41 7 1493 1505 10.1007/s11095‑024‑03732‑z 38918308
    [Google Scholar]
  36. Song Y. Yang P. Guo W. Lu P. Huang C. Cai Z. Jiang X. Yang G. Du Y. Zhao F. Supramolecular hydrogel dexamethasone–diclofenac for the treatment of rheumatoid arthritis. Nanomaterials 2024 14 7 645 10.3390/nano14070645 38607179
    [Google Scholar]
  37. Dodevska T. Shterev I. Nanomaterials as catalysts for the sensitive and selective determination of diclofenac. ADMET DMPK 2023 12 1 151 165 10.5599/admet.2116 38560716
    [Google Scholar]
  38. Dong Q. Guo X. Li L. Yu C. Nie L. Tian W. Zhang H. Huang S. Zang H. Understanding hyaluronic acid induced variation of water structure by near-infrared spectroscopy. Sci. Rep. 2020 10 1 1387 10.1038/s41598‑020‑58417‑5 31992833
    [Google Scholar]
  39. Zhang C. Weng Y. Wang H. Zhan S. Li C. Zheng D. Lin Q. A synergistic effect of triptolide and curcumin on rheumatoid arthritis by improving cell proliferation and inducing cell apoptosis via inhibition of the IL-17/NF-κB signaling pathway. Immunopharmacol. 2024 142 Pt A 112953 10.1016/j.intimp.2024 112953
    [Google Scholar]
  40. Tardito S. Martinelli G. Soldano S. Paolino S. Pacini G. Patane M. Alessandri E. Smith V. Cutolo M. Macrophage M1/M2 polarization and rheumatoid arthritis: A systematic review. Autoimmun. Rev. 2019 18 11 102397 10.1016/j.autrev.2019.102397 31520798
    [Google Scholar]
  41. Feng Y. Pan X. Li Z. Li Y. Sun Y. Yang S. He C. Dang Y. Huang L. Xiang B. Innovative lipid nanoparticles co-delivering hydroxychloroquine and sirna for enhanced rheumatoid arthritis therapy. Pharmaceutics 2025 17 1 45 10.3390/pharmaceutics17010045 39861693
    [Google Scholar]
  42. Chen M. Wang Z. Chen H. Li J. Guo X. Zhou S. Biomimetic nanoparticles inhibit the HIF-1α/iNOS/NLRP3 pathway to alleviate rheumatoid arthritis. Nano Lett. 2025 25 10 3807 3816 10.1021/acs.nanolett.4c05782 40033154
    [Google Scholar]
  43. Choudhary N. Bhatt L.K. Prabhavalkar K.S. Experimental animal models for rheumatoid arthritis. Immunopharmacol. Immunotoxicol. 2018 40 3 193 200 10.1080/08923973.2018.1434793 29433367
    [Google Scholar]
  44. Wang C. Cheng J. Song L. Zhou Z. Zhao Q. Zhao Y. Wang H. Tan Y. Zhao B. Yang M. Self-assembled multilayer-modified needles simulate acupuncture and diclofenac sodium delivery for rheumatoid arthritis. ACS Appl. Mater. Interfaces 2024 16 23 29876 29890 10.1021/acsami.4c04815 38829728
    [Google Scholar]
  45. Xiang L. Huang Q. Chen T. He Q. Yao H. Gao Y. Ethanol extract of Paridis rhizoma attenuates carrageenan-induced paw swelling in rats by inhibiting the production of inflammatory factors. BMC Complement. Med. Ther. 2023 23 1 437 10.1186/s12906‑023‑04264‑6
    [Google Scholar]
  46. Zhang X. Xu X. Chen J. Wang G. Li Q. Li M. Lu J. Identification of HHT-9041P1: A novel potent and selective JAK1 inhibitor in a rat model of rheumatoid arthritis. Immunopharmaco. 2023 125 Pt A 111086 10.1016/j.intimp.2023.111086
    [Google Scholar]
  47. Han Y. Liu C. Chen S. Sun H. Jia Z. Shi J. Wang L. Du K. Chang Y. Columbianadin ameliorates rheumatoid arthritis by attenuating synoviocyte hyperplasia through targeted vimentin to inhibit the VAV2/Rac-1 signaling pathway. J. Adv. Res. 2024 74 609 620 10.1016/j.jare.2024.09.030
    [Google Scholar]
  48. Zhu X.X. Xu A.J. Cai W.W. Han Z.J. Zhang S.J. Hou B. Wen Y.Y. Cao X.Y. Li H.D. Du Y.Q. Zhuang Y.Y. Wang J. Hu X.R. Bai X.R. Su J.B. Zhang A.Y. Lu Q.B. Gu Y. Qiu L.Y. Pan L. Sun H.J. NaHS@Cy5@MS@SP nanoparticles improve rheumatoid arthritis by inactivating the Hedgehog signaling pathway through sustained and targeted release of H2S into the synovium. J. Nanobiotechnology 2025 23 1 192 10.1186/s12951‑025‑03286‑1 40055697
    [Google Scholar]
  49. Chen Y. Xu W. Shafiq M. Song D. Wang T. Yuan Z. Xie X. Yu X. Shen Y. Sun B. Liu Y. Mo X. Injectable nanofiber microspheres modified with metal phenolic networks for effective osteoarthritis treatment. Acta Biomater. 2023 157 593 608 10.1016/j.actbio.2022.11.040 36435438
    [Google Scholar]
  50. Kim D. Kim C. Lee S.E. Kim S. Lee S.I. Park M.H. Kim M. Sung D. Lee K. Development of ros-sensitive sulfasalazine-loaded ferrocene nanoparticles and evaluation of their antirheumatic effects in a 3d synovial hyperplasia model. Small 2025 21 10 e2407813 10.1002/smll.202407813
    [Google Scholar]
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Mesoporous Silica Nanoparticles with Dual Function of Anti-Inflammatory and Lubrication for Rheumatoid Arthritis Treatment
Bentham Science Publishers ; https://doi.org/10.2174/0115672018387431251127045211
/content/journals/cdd/10.2174/0115672018387431251127045211
/content/journals/cdd/10.2174/0115672018387431251127045211
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  • Article Type:     Research Article
Keywords: mesoporous silica nanoparticles ; diclofenac ; inflammation model ; Rheumatoid arthritis ; drug delivery system ; anti-inflammatory

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