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

Abstract

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.

• Authors: Pingju Liu, Liling Gu, Lingyan Ren, Jiajia Chen, Tao Li, Xin Wang, Junjun Yang, Cheng Chen, Li Sun
• Journal: American journal of translational research (Am J Transl Res) Vol. 11 Issue 11 Pg. 6775-6789 ( 2019) ISSN: 1943-8141 [Print] United States
• PMID: 31814887 (Publication Type: Journal Article)
• Copyright: AJTR Copyright © 2019.