Separable microneedles based on thermosensitive hydroxypropyl chitin with hyaluronic acid separation layer via green process for prolonged piroxicam release in osteoarthritis treatment.

Osteoarthritis is a chronic degenerative joint disease with local inflammation that needs sustained, localized anti-inflammatory therapy. In this study, a separable drug-loaded microneedle system based on thermosensitive hydroxypropyl chitin (HPCH) was developed via a green fabrication process without using organic solvents or chemical crosslinkers for prolonged transdermal piroxicam delivery. Each PrxC@HPCH microneedle contained a tip loaded with size-controlled piroxicam microcrystals (PrxC), prepared via an alkaline dissolution-acid neutralization antisolvent strategy, and a rapidly separating dissolving layer, could withstand a compressive force of approximately 1.22 N, sufficient for skin penetration. After insertion, the separation layer rapidly dissolved to detach the tips, which remained in the dermis and formed a physically cross-linked gel depot, enabling sustained piroxicam release in vitro for up to 192 h. Meanwhile, the PrxC@HPCH separable microneedles showed long-lasting anti-inflammatory effects for approximately five days after a single administration in vivo. Importantly, in an osteoarthritis rat model, PrxC@HPCH separable microneedles demonstrated superior and sustained therapeutic efficacy once per 3 days for continuous treatment, with effective suppression of synovitis, preservation of cartilage matrix, and alleviation of subchondral bone deterioration. Overall, this biodegradable HPCH-based separable microneedle platform offers a long-acting strategy for localized osteoarthritis therapy and other chronic inflammatory diseases.