Transdermal Delivery of Baricitinib via Nanosuspension-Loaded Dissolving Microneedles for Rheumatoid Arthritis Therapy

• 1、School of Pharmaceutical Sciences, Medical College of Soochow University, Suzhou 215123

Abstract：Objective: To address the systemic adverse effects and insufficient local drug concentration in joints associated with oral baricitinib for the treatment of rheumatoid arthritis (RA), a dissolving microneedle (DMN)-based transdermal delivery system loaded with baricitinib nanosuspension (BTB-NS@DMNs) was developed to achieve efficient local drug delivery to the joints and reduce systemic toxicity.Methods: Baricitinib nanosuspension (BTB-NS) was prepared using wet media milling and characterized for particle size, morphology, crystallinity, and dissolution behavior. BTB-NS@DMNs were fabricated via a two-step centrifugation method and evaluated for morphology, mechanical strength, skin insertion performance, and intradermal dissolution rate. The in vivo anti-inflammatory efficacy, improvement of joint pathology, and levels of inflammatory cytokines were assessed using an adjuvant-induced arthritis (AIA) rat model.Results: BTB-NS exhibited a mean particle size of 173.66 ± 8.02 nm with a PDI of 0.207 ± 0.025, and the cumulative release reached 89.44 ± 5.72% at 240 min, significantly higher than that of the raw drug. The prepared BTB-NS@DMNs showed excellent morphology and mechanical properties, with a skin insertion rate exceeding 90% and complete intradermal dissolution within 20 min. In the AIA model, BTB-NS@DMNs effectively alleviated paw swelling and ankle thickening, inhibited synovial hyperplasia and cartilage destruction, and reduced pSTAT3 expression as well as TNF-α and IL-6 levels. The local therapeutic efficacy was superior to that of the cream and oral groups, while the systemic anti-inflammatory effect was comparable to that of the oral group.Conclusion: The BTB-NS@DMNs system exhibits favorable formability, mechanical properties, and rapid skin dissolution capability, enabling efficient local delivery of baricitinib to arthritic joints, significantly ameliorating joint inflammation, and reducing systemic exposure. This provides a novel strategy for the local treatment of rheumatoid arthritis.

Keywords： Pharmaceutics Transdermal drug delivery Dissolving microneedles Nanosuspension Baricitinib Rheumatoid arthritis