DHA laden liposome incorporated HA-menthol-CD host-guest hydrogels as delivery system for osteoarthritis treatment

The immobilization of liposomes together laden drugs in the hydrogel matrix network has proven to be an effective technique for protecting them against rapid clearance in the body. This allows for localized and controlled drug delivery over a long period of time. However, the current method has low drug delivery efficiency and the liposomes are not retained for a sufficient duration, which limits its therapeutic effectiveness. To address this issue, we have designed an efficient delivery platform by integrating liposomes with a HA-menthol-CD matrix. This integration leads to the rapid formation of monodisperse HA-menthol-CD@liposome hybrid hydrogels, where the liposomes are securely anchored within the hydrogel through physical network hindrance and non-covalent interactions. The presence of the lipid membrane and the hydrogel matrix network results in a significant extended release of docosahexaenoic acid (DHA) encapsulated in HA-menthol-CD@liposome hydrogels. In vitro studies show that compared to DHA-laden liposomes (Lipo@DHA), DHA-laden HA-menthol-CD@Lipo hydrogels (HA-menthol-CD@Lipo@DHA) can sustain DHA release for over three weeks and promote chondrocyte differentiation of bone marrow mesenchymal stem cells (BMSCs). Furthermore, in vivo experiments demonstrate that injecting HA-menthol-CD@Lipo@DHA into a surgically induced mice osteoarthritis model effectively reduces osteophyte burden, prevents articular cartilage degeneration, and mitigates changes in the subchondral bone. Overall, the HA-menthol-CD@Lipo@DHA hydrogel, as a novel extended delivery platform, shows great potential for the treatment of osteoarthritis.