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Conventional therapeutics for RA, including disease\u2010modifying antirheumatic drugs (DMARDs), nonsteroidal anti\u2010inflammatory drugs (NSAIDs), and corticosteroids, frequently result in unintended adverse effects. Dexamethasone (DEX) is a potent glucocorticoid used to treat RA due to its anti\u2010inflammatory and immunosuppressive properties. Liposomal delivery of DEX, particularly when liposomes are surface\u2010modified with targeting ligands like peptides or sialic acid, can improve drug efficacy by enhancing its distribution to inflamed joints and minimizing toxicity. This study investigates the potential of liposomal drug delivery systems to enhance the efficacy and targeting of DEX in the treatment of RA. Results from various studies demonstrate that liposomal DEX significantly inhibits arthritis progression in animal models, reduces joint inflammation and damage, and alleviates cartilage destruction compared to free DEX. The liposomal formulation also shows better hemocompatibility, fewer adverse effects on body weight and immune organ index, and a longer circulation time with higher bioavailability. The anti\u2010inflammatory mechanism is associated with the downregulation of pro\u2010inflammatory cytokines like tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1) and B\u2010cell\u2013activating factor (BAFF), which are key players in the pathogenesis of RA. Additionally, liposomal DEX can induce the expression of anti\u2010inflammatory cytokines like interleukin\u201010 (IL\u201010), which has significant anti\u2010inflammatory and immunoregulatory properties. The findings suggest that liposomal DEX represents a promising candidate for effective and safe RA therapy, with the potential to improve the management of this debilitating disease by providing targeted delivery and sustained release of the drug.<\/jats:p>","DOI":"10.1002\/ame2.12518","type":"journal-article","created":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T23:40:56Z","timestamp":1733269256000},"page":"5-19","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Improving dexamethasone drug loading and efficacy in treating rheumatoid arthritis via liposome: Focusing on inflammation and molecular mechanisms"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0944-0320","authenticated-orcid":false,"given":"Mohammad Yasin","family":"Zamanian","sequence":"first","affiliation":[{"name":"Department of Physiology, School of Medicine Hamadan University of Medical Sciences  Hamadan Iran"},{"name":"Department of Pharmacology and Toxicology, School of Pharmacy Hamadan University of Medical Sciences  Hamadan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamidreza","family":"Zafari","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Joint Reconstruction Research Center, Imam Khomeini Hospital Complex, School of Medicine Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria K.","family":"Osminina","sequence":"additional","affiliation":[{"name":"Pediatric department I.M. 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