Intra-articular delivery of liposomal celecoxib–hyaluronate combination for the treatment of osteoarthritis in rabbit model

Oral administration of celecoxib (Clx), which is the traditional treatment for osteoarthritis (OA), is accompanied by a high risk for cardiovascular events, while intra-articular injection of hyaluronate (HA) is a well-documented treatment for knee OA. To improve OA therapy while reducing the adverse effects, we formulate Clx-loaded liposomes embedded in HA gel, then administer the liposomal Clx-HA combination via intra-articular injection. Clx-loaded liposomes showed high efficiency encapsulation (>99%). In vitro release studies demonstrated that the release of Clx from lipsosomes was delayed by the combination of HA with liposomes. We examined the effect of intra-articular injection of liposomal Clx-HA combination on cartilage degeneration in rabbit knee OA model. The rabbits were treated with a single intra-articular injection of a single drug, either Clx liposome or HA, or liposomal Clx-HA combination. Using an incapacitance tester and the histopathological study, it was verified that the liposomal Clx-HA combination was more effective than a single drug in pain control and cartilage protection.