MMP13-responsive hydrogel microspheres for osteoarthritis treatment by precise delivery of celecoxib

• DOI: 10.1016/j.matdes.2024.112966
• Publication Date: 2024-04-21T14:12:19Z
• Authors: Honglin Xiang; Chuan Zhang; Yongfu Xiong; Yong Wang; Chaoyu Pu; Jiangtao He; Lu Chen; Ke Jiang; Weikang Zhao; Hanfeng Yang; Fan Wang; Yuling Li
• Keywords: Celecoxib; Hyaluronidase

Osteoarthritis (OA) is characterized by cartilage degradation, inflammatory responses, and osteophyte formation. Matrix metalloproteinase 13 (MMP13) a hallmark of OA development, increased MMP13 expression closely associated with extracellular matrix degradation. varies significantly at different stages progression. While cyclooxygenase 2 (COX-2) inhibitors are commonly used to treat OA, their long-term systemic administration increases the risks adverse effects. Therefore, aim achieving localized responsive delivery COX-2 inhibitor celecoxib, current study investigated an innovative MMP13-responsive micro-nano hydrogel microsphere system. Celecoxib-loaded cationic liposomes non-covalently attached within microsphere, enabling controlled drug release for treatment. In environment elevated expression, system degraded via action substrate peptide (MMP13sp), facilitating accelerated drug-loaded improve microenvironment rapidly. Compared phosphate-buffered saline solution hyaluronidase (HAase), prepared hyaluronic acid methacrylate microspheres HAMA/MMP13sp/Lipo@celecoxib exhibited rapid degradation in containing physiological concentration MMP13/HAase, demonstrating specific enzyme responsiveness precise anti-inflammatory release. The achieves intelligent controllable effectively decelerating disease progression promoting articular repair.