Liposomal dexamethasone for intra-articular therapy: Functional strategies and clinical progress

Intra-articular (IA) injection of dexamethasone (DEX) is an established approach for managing inflammation in arthritis, but it is limited by rapid clearance and short-lived efficacy. Liposomes offer a versatile platform to address these issues by enhancing joint retention and enabling sustained release. This review outlines the pharmacological basis for liposomal DEX in IA therapy and systematically discusses emerging functional strategies to optimize its therapeutic performance. These include leveraging liposome-based lubrication, dual-drug loading for synergistic effects, and stimuli-responsive formulations for on-demand release. We further examine targeting strategies to enhance joint specificity, theranostic liposomes integrating imaging and therapy, and hybrid systems combining liposomes with hydrogels or microspheres for prolonged action. Finally, we highlight the clinical progress of IA liposomal DEX, including approved formulations and ongoing trials, and discuss translational opportunities and challenges. This review provides an integrated perspective on the current status and future directions of liposomal DEX for IA therapy, aiming to inform the development of more durable, targeted, and multifunctional IA corticosteroid systems.