Microneedle Assisted Melittin‐Chondroitin Sulfate Administration for the Transdermal Therapy of Rheumatoid Arthritis

Abstract Rheumatoid arthritis (RA), a persistent and debilitating chronic disease characterize by joint damage and deformity, significantly impairs the life quality of patients and presents challenges for conventional drug administration due to organ damage and unsatisfactory therapeutic outcomes. To address these challenges, this study introduces an innovative hydrogel cryo‐microneedle patch (CMNP)‐mediated local administration system, primarily composed of chondroitin sulfate (CS), to deliver the potent anti‐inflammatory 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‐like synoviocytes (FLS). The MC‐loaded 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‐inflammatory and safe therapy for RA treatment, as well as for other inflammation related chronic diseases.