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Transdermal drug delivery systems for rheumatoid arthritis (RA) have been receiving increasing attention as they can potentially overcome drawbacks which exist in traditional oral or injection strategies, including low patient compliance and serious gastrointestinal side effects. However, transdermal delivery of RA drugs especially biological drugs suffers from low drug delivery efficiency due to the robust skin barrier. Herein, we fabricated melittin-loaded hyaluronic acid (HA) microneedles and investigated their capacity for inhibiting RA. We showed that melittin-loaded HA microneedles possessed high mechanical strength for successful delivery of melittin into the skin and effectively inhibited RA progression in adjuvant induced both rodent and murine models, as shown by results in histological, paw swelling and arthritis score. Furthermore, after modifying HA with cross-linkable groups, the fabricated microneedles with sustained release properties could further improve the therapeutic potency. Cytokine and T cell analysis in the paws and lymphatic organs indicated that the application of microneedles suppressed the levels of pro-inflammation cytokines including IL-17 and TNF-α, and increased the percentage of regulatory CD4 T cells. Our study revealed that polymeric microneedle-mediated transdermal delivery of melittin could serve as a new therapy with high compliance and good therapeutic efficacy for RA and other autoimmune diseases. [Display omitted] [ABSTRACT FROM AUTHOR]

Glucocorticoid (GC) is the cornerstone therapy of rheumatoid arthritis, but high doses are associated with serious adverse effects. In an effort to improve the efficacy of low-dose GC therapy, we developed a micelle system for targeted delivery to inflamed joints and validated the approach in a rat model of arthritis. Micelles loaded with dexamethasone (Dex) self-assembled from the amphipathic poly (ethylene glycol)-block–poly (ε­caprolactone) (PCL–PEG) polymer via film dispersion, and they were injected intravenously at a dose of only 0.8 mg/kg into rats with adjuvant-induced arthritis. The micelles persisted for a relatively long time in the circulation, and they accumulated preferentially in inflamed joints. Micelle-delivered Dex potently reduced joint swelling, bone erosion, and inflammatory cytokine expression in both joint tissue and serum. PCL–PEG micelles caused only moderate adverse effects on body weight, lymphocyte count and blood glucose concentration, and they weakly activated the host complement system. These results suggest that encapsulating Dex in PCL–PEG micelles may allow for safe and effective low-dose GC therapy targeting inflammatory disorders. [ABSTRACT FROM AUTHOR]