Etodolac utility in osteoarthritis: drug delivery challenges, topical nanotherapeutic strategies and potential synergies.

Osteoarthritis (OSA) is a prevalent joint disorder characterized by losing articular cartilage, primarily affecting the hip, knee and spine joints. The impact of OSA offers a major challenge to health systems globally. Therapeutic approaches encompass surgical interventions, non-pharmacological therapies (exercise, rehabilitation, behavioral interventions) and pharmacological treatments. Inflammatory processes within OSA joints are regulated by pro-inflammatory and anti-inflammatory cytokines. Etodolac, a COX-2-selective inhibitor, is the gold standard for OSA management and uniquely does not inhibit gastric prostaglandins. This comprehensive review offers insights into OSA's pathophysiology, genetic factors and biological determinants influencing disease progression. Emphasis is placed on the pivotal role of etodolac in OSA management, supported by both preclinical and clinical evidences in topical drug delivery. Notably, in-silico docking studies suggested potential synergies between etodolac and baicalein, considering ADAMTS-4, COX-2, MMP-3 and MMP-13 as essential therapeutic targets. Integration of artificial neural network (ANN) techniques with nanotechnology approaches emerges as a promising strategy for optimizing and personalizing topical etodolac delivery. Furthermore, the synergistic potential of etodolac and baicalein warrants in-depth exploration. Hence, by embracing cutting-edge technologies like ANN and nanomedicine, the optimization of topical etodolac delivery could guide a new era of OSA treatment.