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, <i>in</i>-<i>silico</i> 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. Osteoarthritis extremely affects the quality of life of people in addition to economic burden on the society. Osteoarthritis influences physical functioning, mental health and social life. Osteoarthritis is a prevalent joint disorder characterized by losing articular cartilage, primarily affecting the hip, knee and spine joints. Magnetic resonance imaging is one of the most promising clinical techniques for diagnosis of osteoarthritis. Biomechanical modeling integrated with artificial intelligence algorithms is advantageous in predicting onset and progression of knee osteoarthritis. Etodolac is the gold standard for osteoarthritis management and does not inhibit gastric prostaglandins. Etodolac has the prospective advantage of not destroying articular cartilage <i>in vivo</i>. Etodolac topical delivery offers reduced side effects and controlled release at the site of action. Addition of lidocaine to etodolac ionic liquid augmented permeation efficiency. Nanoemulsion of etodolac enhanced topical drug delivery to suppress edema. Niosomal etodolac topical gel offered superior anti-inflammatory activity. <i>In-silico</i> docking suggested potential synergies between etodolac and baicalein in osteoarthritis. Integration of artificial neural network techniques with nanotechnology driven drug delivery systems may serve to boost topical etodolac delivery.