Chondroitin sulfate microspheres anchored with drug-loaded liposomes play a dual antioxidant role in the treatment of osteoarthritis.

Reactive oxygen species (ROS) play a critical role in the pathogenesis of osteoarthritis. The injection of a single antioxidant drug is characterized by low drug utilization and short residence time in the articular cavity, limiting the therapeutic effect of antioxidant drugs on osteoarthritis. Currently, the drug circulation half-life can be extended using delivery vehicles such as liposomes and microspheres, which are widely used to treat diseases. In addition, the composite carriers of liposomes and hydrogel microspheres can combine the advantages of different material forms and show stronger plasticity and flexibility than traditional single carriers, which are expected to become new local drug delivery systems. Chondroitin sulfate, a sulfated glycosaminoglycan commonly found in native cartilage, has good antioxidant properties and degradability and is used to develop an injectable chondroitin sulfate hydrogel by covalent modification with photo-cross-linkable methacryloyl groups (ChsMA). Herein, ChsMA microgels anchored with liquiritin (LQ)-loaded liposomes (ChsMA@Lipo) were developed to delay the progression of osteoarthritis by dual antioxidation. On the one hand, the antioxidant drug LQ wrapped in ChsMA@Lipo microgels exhibits significant sustained-release kinetics due to the double obstruction of the lipid membrane and the hydrogel matrix network. On the other hand, ChsMA can eliminate ROS through degradation into chondroitin sulfate monomers by enzymes in vivo. Therefore, ChsMA@Lipo, as a degradable and dual antioxidant drug delivery platform, is a promising option for osteoarthritis treatment. STATEMENT OF SIGNIFICANCE: Compared with the traditional single carrier, the composite carriers of hydrogel microspheres and liposome can complement the advantages of different materials, which shows stronger plasticity and flexibility, and is expected to become a new and efficient drug delivery system. ChsMA@Lipo not only attenuates IL-1β-induced ECM degradation in chondrocytes but also inhibits the M1 macrophages polarization and the inflammasome activation. The obtained ChsMA@Lipo alleviates the progression of osteoarthritis in vivo, which is promising for osteoarthritis treatment.