Intra-articular injection of etoricoxib-loaded PLGA-PEG-PLGA triblock copolymeric nanoparticles attenuates osteoarthritis progression.

The current pharmacological therapies for osteoarthritis (OA) are mainly focused on symptomatic relief of pain and inflammation through the use of nonsteroidal anti-inflammatory drugs (NSAIDs). Etoricoxib is a cyclooxygenase-2 (COX-2) selective NSAID with a higher cyclooxygenase-1 (COX-1) to COX-2 selectivity ratio than the other COX-2 selective NSAIDs and a lower risk of gastrointestinal toxicity compared to traditional NSAIDs. In this study, we first evaluated the anti-inflammatory and chondro-protective effects of etoricoxib on interlecukin-1β-stimulated human osteoarthritic chondrocytes. We found that etoricoxib not only inhibited the expression of inflammation mediators COX-2, prostaglandin E2 (PGE2), and nitric oxide, but also had a similar chondro-protective effect to celecoxib through down-regulating matrix degrading enzymes matrix metalloproteinase-13 (MMP-13) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-5). We then used PLGA-PEG-PLGA triblock copolymeric nanoparticles (NPs) as a drug delivery system to locally deliver etoricoxib into the articular cavity to reduce the risk of cardiovascular toxicity of etoricoxib when administered systemically or orally. The etoricoxib-loaded NPs showed a sustained drug release over 28 days in vitro; in rat OA model, the intra-articular injection of etoricoxib-loaded NPs alleviated the symptoms of subchondral bone, synovium, and cartilage. In conclusion, our study confirmed the chondro-protective role of etoricoxib in OA, and proved the curative effects of etoricoxib-loaded PLGA-PEG-PLGA NPs in vivo.