Synergy between cyclooxygenase-2 inhibitors and hyaluronic acid in the treatment of osteoarthritis: Illumination of signaling cascade, nanotechnology-driven delivery strategies and future prospects

• Published in: Journal of drug delivery science and technology 2024-02, Vol.92, p.105380, Article 105380
• Main Authors: Thote, Samiksha, Gorella, Priyanka, Arya, Shristi, Mourya, Atul, Devangan, Pawan, Jyothi, Vaskuri G.S. Sainaga, Katta, Chantibabu, Singh, Shashi Bala, Mehra, Neelesh Kumar, Madan, Jitender
• Format: Article
• Language: English
• Subjects: Cross-talk; Cyclooxygenase-2 inhibitors; Hyaluronic acid; Osteoarthritis; Signalling cascade; Synergy
• ISSN: 1773-2247
• DOI: 10.1016/j.jddst.2024.105380

Osteoarthritis (OA) is generally caused by a variety of risk factors, the most notable of which are growing age and obesity. Pathophysiologically, chondrocytes alter their morphology and communicate a set of signalling cascades in response to numerous stimuli such as cytokines, chemokines, alarmins, damage-associated molecular patterns, and adipokines. Pharmacological therapies are primarily concerned with symptom alleviation, and no illness-altering OA medication has yet been licensed by regulatory bodies. Hyaluronic acid (HA) is a naturally occurring non-sulphated non-protein glycosaminoglycan entity with distinct physicochemical properties. Interestingly, HA in combination with cyclooxygenase-2 (COX-2) inhibitors has sparked immense attraction due to its viscosupplementation, chondroprotective and anti-inflammatory chattels. The cross-talk of HA with COX-2 inhibitors suppresses the formation of nitric oxide to prevent chondrocyte apoptosis via acting on the MAPK (Mitogen-activated protein kinases) pathway. HA suppresses p38 MAPK activation in profoundly deteriorated chondrocytes and inhibits the translocation and transcription factors. This sequence ultimately impedes the release of pro-inflammatory cytokines and decreases expression of COX-2 enzyme. On the other hand, the viscoelastic property of high molecular weight HA may be attributed to inter-and intra-chain interaction and formation of crosslinks at higher concentrations. Therefore, in the present review, an attempt has been undertaken to unbox the interactions between COX-2 inhibitors and HA. We have also highlighted the key role and merits of COX-2 inhibitors and HA used either alone or in combination, as a vital therapy for OA patients using in-silico docking tools. A plethora of nanotechnology-driven strategies employed to deliver COX-2 inhibitors and HA in the management of OA is also summarized. [Display omitted]