Arbutin-Modified Microspheres Prevent Osteoarthritis Progression by Mobilizing Local Anti-Inflammatory and Antioxidant Responses

Osteoarthritis (OA), a common chronic degenerative disease, is considered the leading cause of disability worldwide. However, the current clinical treatments for OA are still unsatisfactory. Arbutin (ARB) is a major active ingredient of the Chinese medicinal herb cowberry leaf, which exerts potential antioxidant and anti-inflammatory activity. Based on a microfluid platform, we fabricated ARB-loaded gelatine methacryloyl-Liposome (GM-Lipo@ARB) microspheres that showed long-term release and excellent cartilage-targeting effects. The ARB-loaded microspheres effectively reduced the inflammatory response in interleukin (IL)-1β-treated arthritic chondrocytes. Moreover, GM-Lipo@ARB microspheres regulated cartilage extracellular matrix (ECM) homeostasis by upregulating nuclear factor erythroid 2-related factor 2 (Nrf2)-associated antioxidant properties. Intraarticular injection of GM-Lipo@ARB microspheres alleviated cartilage erosion in the destabilization of the medial meniscus (DMM)-mediated mouse OA model. Our results indicated that ARB-modified microspheres prevented cartilage degeneration by not only inhibiting the inflammatory reaction but also mitigating oxidative stress. This study proposes a novel ARB-laden functional microsphere for treating OA through the mobilization of local anti-inflammatory and antioxidant responses.