Celecoxib and shikonin loaded dissolving microneedle exert analgesic, anti-inflammatory and chondroprotective activity for osteoarthritis treatment

Osteoarthritis (OA) is a chronic degenerative disease that severely affects the physical function and quality of life of patients. Non-steroidal anti-inflammatory drugs (NSAIDs) are standard treatments for OA, alleviating joint pain and inflammation. Meanwhile, long-term oral administration and intra-articular injection will bring inevitable side effects. In this study, a dissolving microneedle composite drug delivery system co-loaded with celecoxib and shikonin (SKN-CXB@MN) was prepared, which can efficiently deliver drugs through the skin and exert therapeutic effects on OA from multiple targets including analgesia, anti-inflammation, and cartilage protection.

The material properties of SKN-CXB@MN were assessed through experiments on morphology, mechanical properties, solubility, drug release performance, and skin recovery. The biocompatibility of SKN-CXB@MN was determined using CCK-8 assays and live-dead staining. The protective effect of SKN-CXB@MN on IL-1β-induced chondrocytes were investigated through in vitro anti-apoptosis assays. The analgesic, anti-inflammatory, and cartilage-protective effects of SKN-CXB@MN were evaluated by measuring the joint swelling degree, PWT, weight bearing of RL, histology, and immunohistochemical staining in the OA rat model.

Materials characterization reveals that SKN-CXB@MN possesses sufficient mechanical strength to penetrate the skin. Upon application, the microneedles dissolve completely and release 85% of CXB and 75% of SKN within 15 min . In vitro biocompatibility assays confirm that SKN-CXB@MN is non-cytotoxic to chondrocytes and does not affect cell proliferation. Anti-apoptosis experiments show that SKN-CXB@MN inhibits IL-1β-induced chondrocyte apoptosis. In an OA rat model, SKN-CXB@MN alleviates knee joint swelling and pain, reduces cartilage degeneration, decreases chondrocyte apoptosis, and suppresses the inflammatory response.

The dual-drug loaded SKN-CXB@MN system facilitates targeted drug delivery, thereby reducing systemic side effects. The synergistic effects of Celecoxib (CXB) and Shikonin (SKN) not only substantially alleviate pain and inflammation but also retard cartilage degeneration by modulating chondrocyte apoptosis and extracellular matrix metabolism. These multifaceted mechanisms indicate that the SKN-CXB@MN formulation could be a promising therapeutic option for osteoarthritis management.