Arbutin-modified microspheres prevent osteoarthritis progression by mobilizing local anti-inflammatory and antioxidant responses.

Osteoarthritis (OA) is a common degenerative joint disease worldwide and currently there is no effective strategy to stop its progression. It is known that oxidative stress and inflammation can promote the development of OA, and therapeutic strategies against these conditions may alleviate OA. Arbutin (ARB), a major ingredient of the Chinese medicinal herb cowberry leaf, exerts good antioxidant and anti-inflammatory activities yet has not been studied in OA. Here we developed ARB-loaded gelatine methacryloyl-Liposome (GM-Lipo@ARB) microspheres which showed long-term release of ARB and excellent cartilage-targeting effects. The ARB-loaded microspheres effectively reduced the inflammatory response in interleukin (IL)-1ß-treated arthritic chondrocytes. Moreover, the synthesized GM-Lipo@ARB microspheres regulated cartilage extracellular matrix (ECM) homeostasis through anti-inflammation effect via inhibiting NF-κB signaling and anti-oxidative stress effect via activating Nrf2 pathway. Intra-articular use of GM-Lipo@ARB can effectively reduce inflammation and oxidative stress in the articular cartilage and thus, attenuating OA progression in a mouse model. The study proposed a novel ARB-laden functional microsphere, GM-Lipo@ARB, and demonstrated that this compound may be used as an alternative therapeutics for treating OA.