Microemulsion-embedded hyaluronic acid microneedles improve local triptolide delivery and anti-arthritic efficacy in...

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease characterized by persistent synovial inflammation and progressive cartilage and bone destruction. Triptolide (TP) exhibits potent anti-inflammatory activity, but its therapeutic application is limited by poor aqueous solubility and a narrow therapeutic window. To address these limitations, we developed dissolving hyaluronic acid (HA) microneedles (MNs) incorporating a TP-loaded microemulsion (mean diameter: 27.6 ± 4.4 nm) for local transdermal delivery. The TP-loaded microneedles (TP MNs) showed a uniform pyramidal morphology (height of ∼500 μm) and adequate mechanical strength (fracture force: 0.098 ± 0.010 N per needle), supporting skin insertion with microchannel depths of approximately 450 μm. In vitro, TP MN-derived preparations reduced the viability, migration, and invasion of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS), and decreased inflammatory mediator production, including TNF-α, IL-1β, IL-6, GM-CSF, and CSF-1R. In vivo, TP MNs alleviated joint swelling, synovial hyperplasia, cartilage damage, and bone erosion in a collagen-induced arthritis (CIA) rat model relative to TP HA solution and blank MN controls. At the molecular level, TP-containing treatment was associated with changes in NF-κB-associated downstream readouts in synovial tissues and RA-FLS. Under the present dosing regimen, serum ALT, AST, BUN, and CRE remained comparable among groups, providing preliminary evidence for the absence of overt short-term hepatorenal dysfunction within the study period. Collectively, these results support microemulsion-embedded HA microneedles as a promising local TP delivery platform for inflammatory arthritis, while warranting further investigation of long-term safety, complete pharmacokinetic profiles, and application-site effects.