·
REVIEW
·

Advances in injectable drug delivery systems for the treatment of rheumatoid arthritis

Ying Li1 ,  Qiaojian Duan1 ,  Jinjin Huang2 ,  Peng Zhao1* ,  Kaiyong Cai1*
Show Less
1 Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, China
2 Morgridge College of Education, University of Denver, Denver, CO, USA
BMT 2025 , 6(1), 40–54; https://doi.org/10.12336/biomatertransl.2025.01.004
Submitted: 11 August 2024 | Revised: 4 September 2024 | Accepted: 1 November 2024 | Published: 25 March 2025
Copyright © 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution–NonCommercial–ShareAlike 4.0 License.
Download PDF
Cite
XML
Abstract

Rheumatoid arthritis is a chronic autoimmune disease characterised by inflammation and progressive joint damage, necessitating innovative therapeutic strategies. Conventional rheumatoid arthritis treatments, including disease-modifying antirheumatic drugs, nonsteroidal anti-inflammatory drugs, glucocorticoids, and biologics, often administered through systemic or intra-articular ways. These drugs often have low accumulation and/or retention in articular cartilage, causing dose-limiting toxicities and reduced efficacy. This review summarises recent advances in injectable drug delivery systems, specifically hydrogels, microspheres, and nanoparticles, highlighting their potential to enhance rheumatoid arthritis therapy. The outstanding potential of these systems was demonstrated; however, substantial research remains to be conducted to optimise their performance and safety.

Keywords
hydrogel
microspheres
intra-articular
nanomaterials
rheumatoid arthritis
Funding
This work was financially supported by National Natural Science Foundation of China (Nos. 82102225, and 52333011), National Key Research and Development Program of China (No. 2022YFB3804400), and Venture & Innovation Support Program for Chongqing Overseas Returnees (No. cx2023095).
References

Below is the content of the Citations in the paper which has been de-formatted, however, the content stays consistent with the original.

  1. Conforti, A.; Di Cola, I.; Pavlych, V.; Ruscitti, P.; Berardicurti, O.; Ursini, F.; Giacomelli, R.; Cipriani, P. Beyond the joints, the extra-articular manifestations in rheumatoid arthritis. Autoimmun Rev. 2021, 20, 102735.

 

  1. Nemtsova, M. V.; Zaletaev, D. V.; Bure, I. V.; Mikhaylenko, D. S.; Kuznetsova, E. B.; Alekseeva, E. A.; Beloukhova, M. I.; Deviatkin, A. A.; Lukashev, A. N.; Zamyatnin, A. A., Jr. Epigenetic changes in the pathogenesis of rheumatoid arthritis. Front Genet. 2019, 10, 570.

 

  1. Ciofoaia, E. I.; Pillarisetty, A.; Constantinescu, F. Health disparities in rheumatoid arthritis. Ther Adv Musculoskelet Dis. 2022, 14, 1759720x221137127.

 

  1. Weyand, C. M.; Goronzy, J. J. The immunology of rheumatoid arthritis. Nat Immunol. 2021, 22, 10-18.

 

  1. Porchas-Quijada, M.; Reyes-Castillo, Z.; Muñoz-Valle, J. F.; Durán- Barragán, S.; Aguilera-Cervantes, V.; López-Espinoza, A.; Vázquez-Del Mercado, M.; Navarro-Meza, M.; López-Uriarte, P. IgG anti-ghrelin immune complexes are increased in rheumatoid arthritis patients under biologic therapy and are related to clinical and metabolic markers. Front Endocrinol (Lausanne). 2019, 10, 252.

 

  1. Nygaard, G.; Firestein, G. S. Restoring synovial homeostasis in rheumatoid arthritis by targeting fibroblast-like synoviocytes. Nat Rev Rheumatol. 2020, 16, 316-333.

 

  1. Wu, Z.; Ma, D.; Yang, H.; Gao, J.; Zhang, G.; Xu, K.; Zhang, L. Fibroblast-like synoviocytes in rheumatoid arthritis: Surface markers and phenotypes. Int Immunopharmacol. 2021, 93, 107392.

 

  1. Hannemann, N.; Apparailly, F.; Courties, G. Synovial macrophages: from ordinary eaters to extraordinary multitaskers. Trends Immunol. 2021, 42, 368-371.

 

  1. Croia, C.; Bursi, R.; Sutera, D.; Petrelli, F.; Alunno, A.; Puxeddu, I. One year in review 2019: pathogenesis of rheumatoid arthritis. Clin Exp Rheumatol. 2019, 37, 347-357.

 

  1. Scherer, H. U.; Häupl, T.; Burmester, G. R. The etiology of rheumatoid arthritis. J Autoimmun. 2020, 110, 102400.

 

  1. Fraenkel, L.; Bathon, J. M.; England, B. R.; St Clair, E. W.; Arayssi, T.; Carandang, K.; Deane, K. D.; Genovese, M.; Huston, K. K.; Kerr, G.; Kremer, J.; Nakamura, M. C.; Russell, L. A.; Singh, J. A.; Smith, B. J.; Sparks, J. A.; Venkatachalam, S.; Weinblatt, M. E.; Al-Gibbawi, M.; Baker, J. F.; Barbour, K. E.; Barton, J. L.; Cappelli, L.; Chamseddine, F.; George, M.; Johnson, S. R.; Kahale, L.; Karam, B. S.; Khamis, A. M.; Navarro-Millán, I.; Mirza, R.; Schwab, P.; Singh, N.; Turgunbaev, M.; Turner, A. S.; Yaacoub, S.; Akl, E. A. 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken). 2021, 73, 924-939.

 

  1. Rai, P. K.; Sharma, V.; Mukharjee, J.; Dhote, V. V. A brief review on inflammatory mediators and drug therapy for rheumatoid arthritis. Trends Drug Deliv. 2019, 6, 1-4.

 

  1. Khalil, N. Y.; Aldosari, K. F. Meloxicam. Profiles Drug Subst Excip Relat Methodol. 2020, 45, 159-197.

 

  1. Khan, S.; Andrews, K. L.; Chin-Dusting, J. P. F. Cyclo-oxygenase (COX) inhibitors and cardiovascular risk: are non-steroidal anti-inflammatory drugs really anti-inflammatory? Int J Mol Sci. 2019, 20, 4262.

 

  1. Paglia, M. D. G.; Silva, M. T.; Lopes, L. C.; Barberato-Filho, S.; Mazzei, L. G.; Abe, F. C.; de Cássia Bergamaschi, C. Use of corticoids and non-steroidal anti-inflammatories in the treatment of rheumatoid arthritis: Systematic review and network meta-analysis. PLoS One. 2021, 16, e0248866.

 

  1. Xie, P.; Xue, W.; Qi, W.; Li, Y.; Yang, L.; Yang, Z.; Shi, A. Safety, tolerability, and pharmacokinetics of ibuprofenamine hydrochloride spray (NSAIDs), a new drug for rheumatoid arthritis and osteoarthritis, in healthy Chinese subjects. Drug Des Devel Ther. 2021, 15, 629-638.

 

  1. Bahap-Kara, M.; Sariyildiz, E.; Yardimci, G. K.; Karadag, O.; Bayraktar- Ekincioglu, A. Addressing glucocorticoid-related problems with the clinical pharmacist collaboration in rheumatology practice: a prospective follow-up study. Rheumatol Ther. 2024, 11, 1043-1055.

 

  1. Xu, W.; Ye, J.; Cao, Z.; Zhao, Y.; Zhu, Y.; Li, L. Glucocorticoids in lung cancer: Navigating the balance between immunosuppression and therapeutic efficacy. Heliyon. 2024, 10, e32357.

 

  1. Song, S.; Wang, Y.; Fang, Y.; Teng, F.; Yue, T.; Chen, L.; Wan, X.; Hong, R.; Xue, M. Glucocorticoids promote joint microenvironment alteration of GABBR1 expression associated with mitigating rheumatoid arthritis. Cell Mol Biol (Noisy-le-grand). 2024, 70, 73-77.

 

  1. Hua, C.; Buttgereit, F.; Combe, B. Glucocorticoids in rheumatoid arthritis: current status and future studies. RMD Open. 2020, 6, e000536.

 

  1. Coburn, B. W.; Baker, J. F.; Hsu, J. Y.; Wu, Q.; Xie, F.; Curtis, J. R.; George, M. D. Association of cardiovascular outcomes with low-dose glucocorticoid prescription in patients with rheumatoid arthritis. Arthritis Rheumatol. 2024, 76, 1585-1593.

 

  1. Smolen, J. S.; Landewé, R. B. M.; Bergstra, S. A.; Kerschbaumer, A.; Sepriano, A.; Aletaha, D.; Caporali, R.; Edwards, C. J.; Hyrich, K. L.; Pope, J. E.; de Souza, S.; Stamm, T. A.; Takeuchi, T.; Verschueren, P.; Winthrop, K. L.; Balsa, A.; Bathon, J. M.; Buch, M. H.; Burmester, G. R.; Buttgereit, F.; Cardiel, M. H.; Chatzidionysiou, K.; Codreanu, C.; Cutolo, M.; den Broeder, A. A.; El Aoufy, K.; Finckh, A.; Fonseca, J. E.; Gottenberg, J. E.; Haavardsholm, E. A.; Iagnocco, A.; Lauper, K.; Li, Z.; McInnes, I. B.; Mysler, E. F.; Nash, P.; Poor, G.; Ristic, G. G.; Rivellese, F.; Rubbert-Roth, A.; Schulze-Koops, H.; Stoilov, N.; Strangfeld, A.; van der Helm-van Mil, A.; van Duuren, E.; Vliet Vlieland, T. P. M.; Westhovens, R.; van der Heijde, D. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis. 2023, 82, 3-18.

 

  1. Alfaro-Lara, R.; Espinosa-Ortega, H. F.; Arce-Salinas, C. A. Systematic review and meta-analysis of the efficacy and safety of leflunomide and methotrexate in the treatment of rheumatoid arthritis. Reumatol Clin (Engl Ed). 2019, 15, 133-139.

 

  1. Fleischmann, R.; Takeuchi, T.; Schiff, M.; Schlichting, D.; Xie, L.; Issa, M.; Stoykov, I.; Lisse, J.; Martinez-Osuna, P.; Rooney, T.; Zerbini, C. A. F. Efficacy and safety of long-term baricitinib with and without methotrexate for the treatment of rheumatoid arthritis: experience with baricitinib monotherapy continuation or after switching from methotrexate monotherapy or baricitinib plus methotrexate. Arthritis Care Res (Hoboken). 2020, 72, 1112-1121.

 

  1. Radu, A. F.; Bungau, S. G. Management of rheumatoid arthritis: an overview. Cells. 2021, 10, 2857.

 

  1. García-González, C. M.; Baker, J. Treatment of early rheumatoid arthritis: Methotrexate and beyond. Curr Opin Pharmacol. 2022, 64, 102227.

 

  1. Patra, S.; Choudhury, T. P.; Barman, S. The journey of methotrexate and potential alternative pharmacotherapies for rheumatoid arthritis. Curr Drug Res Rev. 2024. doi: 10.2174/01258997752586342312260522 04.

 

  1. Dickson, K. S.; Regan, A.; Wemyss, C.; Paley, M.; Siddiqui, A. A call for guidance on the treatment of patients taking disease-modifying anti-rheumatic drugs (DMARDs). Br J Oral Maxillofac Surg. 2024, 62, 389-390.

 

  1. Cronstein, B. N.; Aune, T. M. Methotrexate and its mechanisms of action in inflammatory arthritis. Nat Rev Rheumatol. 2020, 16, 145-154.

 

  1. Wang, Z.; Huang, J.; Xie, D.; He, D.; Lu, A.; Liang, C. Toward overcoming treatment failure in rheumatoid arthritis. Front Immunol. 2021, 12, 755844.

 

  1. Hamed, K. M.; Dighriri, I. M.; Baomar, A. F.; Alharthy, B. T.; Alenazi, F. E.; Alali, G. H.; Alenazy, R. H.; Alhumaidi, N. T.; Alhulayfi, D. H.; Alotaibi, Y. B.; Alhumaidan, S. S.; Alhaddad, Z. A.; Humadi, A. A.; Alzahrani, S. A.; Alobaid, R. H. Overview of methotrexate toxicity: a comprehensive literature review. Cureus. 2022, 14, e29518.

 

  1. Bellinvia, S.; Cummings, J. R. F.; Ardern-Jones, M. R.; Edwards, C. J. Adalimumab biosimilars in europe: an overview of the clinical evidence. Biodrugs. 2019, 33, 241-253.

 

  1. Subedi, S.; Gong, Y.; Chen, Y.; Shi, Y. Infliximab and biosimilar infliximab in psoriasis: efficacy, loss of efficacy, and adverse events. Drug Des Devel Ther. 2019, 13, 2491-2502.

 

  1. Atiqi, S.; Hooijberg, F.; Loeff, F. C.; Rispens, T.; Wolbink, G. J. Immunogenicity of TNF-Inhibitors. Front Immunol. 2020, 11, 312.

 

  1. Rai, V.; Patel, N.; Mammen, S. R.; Chaudhary, S. M.; Arshad, S.; Munazzam, S. W. Futuristic novel therapeutic approaches in the treatment of rheumatoid arthritis. Cureus. 2023, 15, e49738.

 

  1. Kubo, S.; Nakayamada, S.; Tanaka, Y. Baricitinib for the treatment of rheumatoid arthritis and systemic lupus erythematosus: a 2019 update. Expert Rev Clin Immunol. 2019, 15, 693-700.

 

  1. Song, P.; Cui, Z.; Hu, L. Applications and prospects of intra-articular drug delivery system in arthritis therapeutics. J Control Release. 2022, 352, 946-960.

 

  1. de la Torre-Aboki, J.; Uson, J.; Pitsillidou, I.; Vardanyan, V.; Nikiphorou, E.; Rodriguez-Garcia, S. C.; Castellanos-Moreira, R.; Pandit, H.; O’Neill, T. W.; Doherty, M.; Boesen, M.; Möller, I.; Terslev, L.; D’Agostino, M. A.; Kampen, W. U.; Berenbaum, F.; Naredo, E.; Carmona, L. Intra-articular therapies: patient preferences and professional practices in European countries. Rheumatol Int. 2022, 42, 869-878.

 

  1. Gardner, J. E.; Williams, C. W.; Bowers, R. L. Subchondral versus intra-articular orthobiologic injections for the treatment of knee osteoarthritis: a review. Regen Med. 2022, 17, 389-400.

 

  1. Ma, L.; Zheng, X.; Lin, R.; Sun, A. R.; Song, J.; Ye, Z.; Liang, D.; Zhang, M.; Tian, J.; Zhou, X.; Cui, L.; Liu, Y.; Liu, Y. Knee osteoarthritis therapy: recent advances in intra-articular drug delivery systems. Drug Des Devel Ther. 2022, 16, 1311-1347.

 

  1. Kolasinski, S. L.; Neogi, T.; Hochberg, M. C.; Oatis, C.; Guyatt, G.; Block, J.; Callahan, L.; Copenhaver, C.; Dodge, C.; Felson, D.; Gellar, K.; Harvey, W. F.; Hawker, G.; Herzig, E.; Kwoh, C. K.; Nelson, A. E.; Samuels, J.; Scanzello, C.; White, D.; Wise, B.; Altman, R. D.; DiRenzo, D.; Fontanarosa, J.; Giradi, G.; Ishimori, M.; Misra, D.; Shah, A. A.; Shmagel, A. K.; Thoma, L. M.; Turgunbaev, M.; Turner, A. S.; Reston, J. 2019 American College of Rheumatology/Arthritis Foundation guideline for the management of osteoarthritis of the hand, hip, and knee. Arthritis Care Res (Hoboken). 2020, 72, 149-162.

 

  1. Mordin, M.; Parrish, W.; Masaquel, C.; Bisson, B.; Copley-Merriman, C. Intra-articular hyaluronic acid for osteoarthritis of the knee in the united states: a systematic review of economic evaluations. Clin Med Insights Arthritis Musculoskelet Disord. 2021, 14, 11795441211047284.

 

 

  1. Guarise, C.; Tessari, M.; Pavan, M.; Pluda, S.; Di Lucia, A.; Barbera, C.; Galesso, D. Hydrophobic derivatives of sulfated hyaluronic acid as drug delivery systems for multi-target intra-articular treatment of post-traumatic osteoarthritis. J Pharm Sci. 2022, 111, 2505-2513.

 

  1. Marinho, A.; Nunes, C.; Reis, S. Hyaluronic acid: a key ingredient in the therapy of inflammation. 2021, 11, 1518.

 

  1. Le Merdy, M.; Mullin, J.; Lukacova, V. Development of PBPK model for intra-articular injection in human: methotrexate solution and rheumatoid arthritis case study. J Pharmacokinet Pharmacodyn. 2021, 48, 909-922.

 

  1. Salaffi, F.; Di Carlo, M.; Farah, S.; Carotti, M. Adherence to subcutaneous anti-TNFα agents in patients with rheumatoid arthritis is largely influenced by pain and skin sensations at the injection site. Int J Rheum Dis. 2020, 23, 480-487.

 

  1. Bullock, J.; Rizvi, S. A. A.; Saleh, A. M.; Ahmed, S. S.; Do, D. P.; Ansari, R. A.; Ahmed, J. Rheumatoid arthritis: a brief overview of the treatment. Med Princ Pract. 2018, 27, 501-507.

 

  1. Dwivedi, S.; Testa, E. J.; Modest, J. M.; Ibrahim, Z.; Gil, J. A. Surgical management of rheumatoid arthritis of the hand. R I Med J (2013). 2020, 103, 32-36.

 

  1. Liu, G.; Zhou, Y.; Xu, Z.; Bao, Z.; Zheng, L.; Wu, J. Janus hydrogel with dual antibacterial and angiogenesis functions for enhanced diabetic wound healing. Chin Chem Lett. 2023, 34, 107705.

 

  1. Zhang, Z.; Hao, Z.; Xian, C.; Zhang, J.; Wu, J. Triple functional magnesium ascorbyl phosphate encapsulated hydrogel: A cosmetic ingredient promotes bone repair via anti-oxidation, calcium uptake and blood vessel remodeling. Chem Eng J. 2023, 472, 145061.

 

  1. Chapa-Villarreal, F. A.; Stephens, M.; Pavlicin, R.; Beussman, M.; Peppas, N. A. Therapeutic delivery systems for rheumatoid arthritis based on hydrogel carriers. Adv Drug Deliv Rev. 2024, 208, 115300.

 

  1. Zewail, M.; Nafee, N.; Helmy, M. W.; Boraie, N. Synergistic and receptor-mediated targeting of arthritic joints via intra-articular injectable smart hydrogels containing leflunomide-loaded lipid nanocarriers. Drug Deliv Transl Res. 2021, 11, 2496-2519.

 

  1. Bernhard, S.; Tibbitt, M. W. Supramolecular engineering of hydrogels for drug delivery. Adv Drug Deliv Rev. 2021, 171, 240-256.

 

  1. Wu, Y.; Ge, Y.; Wang, Z.; Zhu, Y.; Tian, T.; Wei, J.; Jin, Y.; Zhao, Y.; Jia, Q.; Wu, J.; Ge, L. Synovium microenvironment-responsive injectable hydrogel inducing modulation of macrophages and elimination of synovial fibroblasts for enhanced treatment of rheumatoid arthritis. J Nanobiotechnology. 2024, 22, 188.

 

  1. Liu, X.; Zhang, Q.; Cao, Y.; Hussain, Z.; Xu, M.; Liu, Y.; Ullah, I.; Lu, Z.; Osaka, A.; Lin, J.; Pei, R. An injectable hydrogel composing anti-inflammatory and osteogenic therapy toward bone erosions microenvironment remodeling in rheumatoid arthritis. Adv Healthc Mater. 2024, 13, e2304668.

 

  1. Wu, H.; Wang, K.; Wang, H.; Chen, F.; Huang, W.; Chen, Y.; Chen, J.; Tao, J.; Wen, X.; Xiong, S. Novel self-assembled tacrolimus nanoparticles cross-linking thermosensitive hydrogels for local rheumatoid arthritis therapy. Colloids Surf B Biointerfaces. 2017, 149, 97-104.

 

  1. Wu, Y.; Wang, Z.; Ge, Y.; Zhu, Y.; Tian, T.; Wei, J.; Jin, Y.; Zhao, Y.; Jia, Q.; Wu, J.; Ge, L. Microenvironment responsive hydrogel exerting inhibition of cascade immune activation and elimination of synovial fibroblasts for rheumatoid arthritis therapy. J Control Release. 2024, 370, 747-762.

 

  1. Geng, W.; Zhao, J.; Tao, B.; Yang, Y.; Duan, Q.; Gao, P.; He, T.; Liu, S.; Feng, Q.; Zhao, P.; Cai, K. Regulation of rheumatoid arthritis microenvironment via a self-healing injectable hydrogel for improved inflammation elimination and bone repair. Bioact Mater. 2024, 36, 287- 300.

 

  1. Wang, N.; Ma, J.; Song, W.; Zhao, C. An injectable hydrogel to disrupt neutrophil extracellular traps for treating rheumatoid arthritis. Drug Deliv. 2023, 30, 2173332.

 

  1. Shah, D. K.; Ghosh, S.; More, N.; Choppadandi, M.; Sinha, M.; Srivalliputtur, S. B.; Velayutham, R.; Kapusetti, G. ECM-mimetic, NSAIDs loaded thermo-responsive, immunomodulatory hydrogel for rheumatoid arthritis treatment. BMC Biotechnol. 2024, 24, 26.

 

  1. Yu, Z.; Xu, Q.; Dong, C.; Lee, S. S.; Gao, L.; Li, Y.; D’Ortenzio, M.; Wu, J. Self-assembling peptide nanofibrous hydrogel as a versatile drug delivery platform. Curr Pharm Des. 2015, 21, 4342-4354.

 

  1. Yi, J.; Liu, Y.; Xie, H.; An, H.; Li, C.; Wang, X.; Chai, W. Hydrogels for the treatment of rheumatoid arthritis. Front Bioeng Biotechnol. 2022, 10, 1014543.

 

  1. Wang, S.; Qiu, Y.; Qu, L.; Wang, Q.; Zhou, Q. Hydrogels for treatment of different degrees of osteoarthritis. Front Bioeng Biotechnol. 2022, 10, 858656.

 

  1. Miao, K.; Zhou, Y.; He, X.; Xu, Y.; Zhang, X.; Zhao, H.; Zhou, X.; Gu, Q.; Yang, H.; Liu, X.; Huang, L.; Shi, Q. Microenvironment-responsive bilayer hydrogel microspheres with gelatin-shell for osteoarthritis treatment. Int J Biol Macromol. 2024, 261, 129862.

 

  1. Liu, J.; Zhou, Z.; Hou, M.; Xia, X.; Liu, Y.; Zhao, Z.; Wu, Y.; Deng, Y.; Zhang, Y.; He, F.; Xu, Y.; Zhu, X. Capturing cerium ions via hydrogel microspheres promotes vascularization for bone regeneration. Mater Today Bio. 2024, 25, 100956.

 

  1. Wei, L.; Pan, Q.; Teng, J.; Zhang, H.; Qin, N. Intra-articular administration of PLGA resveratrol sustained-release nanoparticles attenuates the development of rat osteoarthritis. Mater Today Bio. 2024, 24, 100884.

 

  1. Rajesh, K.; Khatua, C.; Singh, P.; Roy, P.; Keshri, A. K.; Lahiri, D. Microsphere embedded hydroxyapatite coating on metallic implant for sustained drug release in orthopedic applications. J Drug Deliv Sci Technol. 2024, 98, 105840.

 

  1. Xiao, P.; Han, X.; Huang, Y.; Yang, J.; Chen, L.; Cai, Z.; Hu, N.; Cui, W.; Huang, W. Reprogramming macrophages via immune cell mobilized hydrogel microspheres for osteoarthritis treatments. Bioact Mater. 2024, 32, 242-259.

 

  1. Singh, R.; Jadhav, K.; Kamboj, R.; Malhotra, H.; Ray, E.; Jhilta, A.; Dhir, V.; Verma, R. K. Self-actuating inflammation responsive hydrogel microsphere formulation for controlled drug release in rheumatoid arthritis (RA): Animal trials and study in human fibroblast like synoviocytes (hFLS) of RA patients. Biomater Adv. 2024, 160, 213853.

 

  1. Li, C.; Du, Y.; Lv, H.; Zhang, J.; Zhuang, P.; Yang, W.; Zhang, Y.; Wang, J.; Cui, W.; Chen, W. Injectable amphipathic artesunate prodrug-hydrogel microsphere as gene/drug nano-microplex for rheumatoid arthritis therapy. Adv Funct Mater. 2022, 32, 2206261.

 

  1. Yao, Y.; Wei, G.; Ding, J.; Cui, W. Injectable hydrogel microspheres experimental research for the treatment of osteoarthritis. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2023, 37, 918-928.

 

  1. Morici, L.; Gonzalez-Fernandez, P.; Jenni, S.; Porcello, A.; Allémann, E.; Jordan, O.; Rodríguez-Nogales, C. Nanocrystal-chitosan particles for intra-articular delivery of disease-modifying osteoarthritis drugs. Int J Pharm. 2024, 651, 123754.

 

  1. Peng, X.; Dai, Z.; Zhang, Q.; Gao, S.; Li, N. Intelligent microsphere-gel structures: Pioneering multi-range temperature sensing technology. Appl Mater Today. 2024, 38, 102244.

 

  1. An, X.; Zhou, F.; Li, G.; Wei, Y.; Huang, B.; Li, M.; Zhang, Q.; Xu, K.; Zhao, R. C.; Su, J. Cyaonoside A-loaded composite hydrogel microspheres to treat osteoarthritis by relieving chondrocyte inflammation. J Mater Chem B. 2024, 12, 4148-4161.

 

  1. Butreddy, A.; Gaddam, R. P.; Kommineni, N.; Dudhipala, N.; Voshavar, C. PLGA/PLA-based long-acting injectable depot microspheres in clinical use: production and characterization overview for protein/ peptide delivery. Int J Mol Sci. 2021, 22, 8884.

 

  1. Liu, Y.; Cao, F.; Sun, B.; Bellanti, J. A.; Zheng, S. G. Magnetic nanoparticles: A new diagnostic and treatment platform for rheumatoid arthritis. J Leukoc Biol. 2021, 109, 415-424.

 

  1. Wong, X. Y.; Sena-Torralba, A.; Álvarez-Diduk, R.; Muthoosamy, K.; Merkoçi, A. Nanomaterials for nanotheranostics: tuning their properties according to disease needs. ACS Nano. 2020, 14, 2585-2627.

 

  1. Han, Y.; Huang, S. Nanomedicine is more than a supporting role in rheumatoid arthritis therapy. J Control Release. 2023, 356, 142-161.

 

  1. Radu, A. F.; Bungau, S. G. Nanomedical approaches in the realm of rheumatoid arthritis. Ageing Res Rev. 2023, 87, 101927.

 

  1. Geng, W.; Liu, X.; Tao, B.; He, Y.; Li, K.; Gao, P.; Feng, Q.; Zhao, P.; Luo, Z.; Cai, K. Nitric oxide scavenging and hydrogen sulfide production synergistically treat rheumatoid arthritis. Adv Healthc Mater. 2023, 12, e2202380.

 

  1. Gandhi, S.; Shende, P. Anti-CD64 antibody-conjugated PLGA nanoparticles containing methotrexate and gold for theranostics application in rheumatoid arthritis. AAPS PharmSciTech. 2024, 25, 22.

 

  1. Han, X.; Song, P.; Cai, R.; Zhu, H.; Yan, J.; Wang, X.; Wang, Y.; Kang, Y.; Ma, Y.; Wang, L.; Zhang, H. Construction of janus mesenchymal stem cell-hitchhiked melanin nanoparticles to modulate the Th17/Treg balance for rheumatoid arthritis therapy. Nano Today. 2024, 57, 102322.

 

  1. Wu, Y. Z.; Chen, W. Y.; Zeng, Y.; Ji, Q. L.; Yang, Y.; Guo, X. L.; Wang, X. Inflammation-responsive mesoporous silica nanoparticles with synergistic anti-inflammatory and joint protection effects for rheumatoid arthritis treatment. Pharm Res. 2024, 41, 1493-1505.

 

  1. Gan, J.; Huang, D.; Che, J.; Zhao, Y.; Sun, L. Biomimetic nanoparticles with cell-membrane camouflage for rheumatoid arthritis. 2024, 7, 794-825.

 

  1. Hao, X.; Gai, W.; Zhang, Y.; Zhou, W.; Feng, Y. Biomimetic and inflammation-targeted nanoparticles for rheumatoid arthritis therapy via M1-macrophages apoptosis and polarization. Mater Des. 2024, 239, 112806.

 

  1. Dhiman, N.; Sarvaiya, J.; Mohindroo, P. A drift on liposomes to proliposomes: recent advances and promising approaches. J Liposome Res. 2022, 32, 317-331.

 

  1. Filipczak, N.; Pan, J.; Yalamarty, S. S. K.; Torchilin, V. P. Recent advancements in liposome technology. Adv Drug Deliv Rev. 2020, 156, 4-22.

 

  1. Monteiro, N.; Martins, A.; Reis, R. L.; Neves, N. M. Liposomes in tissue engineering and regenerative medicine. J R Soc Interface. 2014, 11, 20140459.

 

  1. Haider, M.; Abdin, S. M.; Kamal, L.; Orive, G. Nanostructured lipid carriers for delivery of chemotherapeutics: a review. 2020, 12, 288.

 

  1. Fu, X.; Song, Y.; Feng, X.; Liu, Z.; Gao, W.; Song, H.; Zhang, Q. Synergistic chemotherapy/PTT/oxygen enrichment by multifunctional liposomal polydopamine nanoparticles for rheumatoid arthritis treatment. Asian J Pharm Sci. 2024, 19, 100885.

 

  1. Guo, R. B.; Kong, L.; Yu, Y.; Liu, Y.; Zhang, L.; Qu, X. W.; Li, S. T.; Yu, J. J.; Li, X. T.; Li, X. Y. Matrix metalloproteinase-sensitive size-shrinkable liposomes targeting activated macrophages for the treatment of rheumatoid arthritis. Appl Mater Today. 2024, 38, 102182.

 

  1. Zhang, L.; Qin, Z.; Sun, H.; Chen, X.; Dong, J.; Shen, S.; Zheng, L.; Gu, N.; Jiang, Q. Nanoenzyme engineered neutrophil-derived exosomes attenuate joint injury in advanced rheumatoid arthritis via regulating inflammatory environment. Bioact Mater. 2022, 18, 1-14.

 

  1. Mondal, J.; Pillarisetti, S.; Junnuthula, V.; Saha, M.; Hwang, S. R.; Park, I. K.; Lee, Y. K. Hybrid exosomes, exosome-like nanovesicles and engineered exosomes for therapeutic applications. J Control Release. 2023, 353, 1127-1149.

 

  1. Jiang, X.; Shi, L.; Feng, H.; Zhang, Y.; Dong, J.; Shen, Z. Engineered exosomes loaded with triptolide: an innovative approach to enhance therapeutic efficacy in rheumatoid arthritis. Int Immunopharmacol. 2024, 129, 111677.

 

  1. Liu, H.; Li, R.; Liu, T.; Yang, L.; Yin, G.; Xie, Q. Immunomodulatory effects of mesenchymal stem cells and mesenchymal stem cell-derived extracellular vesicles in rheumatoid arthritis. Front Immunol. 2020, 11, 1912.

 

  1. Wang, S.; Lei, B.; Zhang, E.; Gong, P.; Gu, J.; He, L.; Han, L.; Yuan, Z. Targeted therapy for inflammatory diseases with mesenchymal stem cells and their derived exosomes: from basic to clinics. Int J Nanomedicine. 2022, 17, 1757-1781.

 

  1. Su, Y.; Liu, Y.; Ma, C.; Guan, C.; Ma, X.; Meng, S. Mesenchymal stem cell-originated exosomal lncRNA HAND2-AS1 impairs rheumatoid arthritis fibroblast-like synoviocyte activation through miR-143-3p/ TNFAIP3/NF-κB pathway. J Orthop Surg Res. 2021, 16, 116.

 

  1. Zhang, S.; Duan, Z.; Liu, F.; Wu, Q.; Sun, X.; Ma, H. The impact of exosomes derived from distinct sources on rheumatoid arthritis. Front Immunol. 2023, 14, 1240747.

 

  1. Xiao, S.; Tang, Y.; Lv, Z.; Lin, Y.; Chen, L. Nanomedicine - advantages for their use in rheumatoid arthritis theranostics. J Control Release. 2019, 316, 302-316.

 

  1. Abdel-Hakem, N. E.; Talaat, R. M.; Samaka, R. M.; Bassyouniy, I. H.; El-Shahat, M.; Alkawareek, M. Y.; Alkilany, A. M. Therapeutic outcomes and biodistribution of gold nanoparticles in collagen-induced arthritis animal model. J Drug Deliv Sci Technol. 2022, 67, 102944.

 

  1. Song, Y.; Su, Y.; Hussain, S. A.; Tang, C. Resveratrol and prednisolone loaded into human serum albumin nanoparticles for the alleviation of rheumatoid arthritis symptoms: an in vitro and in vivo study. Mater Sci Poland. 2024, 42, 16-25.

 

  1. Ma, L.; Jiang, X.; Gao, J. Revolutionizing rheumatoid arthritis therapy: harnessing cytomembrane biomimetic nanoparticles for novel treatment strategies. Drug Deliv Transl Res. 2025, 15, 66-83.
Conflict of interest
The authors declare no conflict of interest.
Share
Back to top
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here
Accept