Recent Advancements of Hyaluronic Acid Nanoscaffolds in Arthritis Management

Abstract Arthritis is a significant health concern affecting over 528 million people globally, reducing quality of life. The chronic nature of arthritis, coupled with insufficient therapeutic effectiveness, recurrence, and adverse side effects, complicates its management. Hyaluronic acid (HA) has emerged as a promising solution due to its biocompatibility, non‐toxicity, and targeted drug delivery capabilities, being a key component of the cartilage extracellular matrix widely used in managing arthritis. HA's inherent viscoelastic property and ability to target CD44 have spurred interest in developing HA‐based systems for delivering drugs to manage arthritis. Hyaluronic acid nanoscaffolds (HA‐NSCfs) show improved outcomes over treatments, including enhanced drug uptake through receptor‐mediated targeting, prolonged retention in the synovium, reduced proinflammatory mediator expression, enhanced cartilage regeneration, reduced drug toxicity due to sustained release, and more cost‐effective treatments. This review highlights the rationale for using HA‐NSCfs for the management and advanced drug delivery systems in arthritis, emphasizing preclinical and clinical results. It discusses various solid‐lipid nanoparticles, hydroxyapatite nanoparticles, polyelectrolyte complexes, liposomes, bilosomes, drug‐polymer conjugates, hydrogels, inorganic nanoparticles, and polymer nanoparticles, etc reported for arthritis management. Additionally, the review identifies key challenges and offers suggestions to address them, ultimately highlighting the potential of HA‐NSCfs as a topical treatment for arthritis.