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To address these challenges, this study introduces an innovative hydrogel cryo\u2010microneedle patch (CMNP)\u2010mediated local administration system, primarily composed of chondroitin sulfate (CS), to deliver the potent anti\u2010inflammatory drug melittin (MEL). This innovative approach not only circumvents organ impairment but also enhances patient compliance. The acute toxicity of MEL is effectively mitigated by electrostatic binding with CS molecules, forming MC complexes that induce apoptosis in fibroblast\u2010like synoviocytes (FLS). The MC\u2010loaded CMNPs (MC@CCMNPs) exhibit remarkable therapeutic capacity with a notably meliorated joint damage and suppressed arthritis severity in the RA rat model. Therefore, MC@CCMNPs emerge as a promising anti\u2010inflammatory and safe therapy for RA treatment, as well as for other inflammation related chronic diseases.<\/jats:p>","DOI":"10.1002\/adhm.202400543","type":"journal-article","created":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T00:36:11Z","timestamp":1740011771000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Microneedle Assisted Melittin\u2010Chondroitin Sulfate Administration for the Transdermal Therapy of Rheumatoid Arthritis"],"prefix":"10.1002","volume":"14","author":[{"given":"Lili","family":"Jin","sequence":"first","affiliation":[{"name":"Frontiers Science Center for Materiobiology and Dynamic Chemistry East China University of Science and Technology  Shanghai 200237 P. R. China"},{"name":"Engineering Research Center for Biomedical Materials of Ministry of Education East China University of Science and Technology  Shanghai 200237 P. R. 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