Sustained-release local anesthetics: advances in drug delivery systems for prolonged postoperative analgesia

Effective perioperative pain control is essential for patient comfort and for optimizing surgical outcomes and the quality of recovery. Multimodal analgesic strategies have become a cornerstone of modern perioperative pain management. Although regional analgesia is widely used within this framework, the clinical utility of conventional local anesthetics remains limited by their relatively short duration of action. Continuous infusion techniques can sustain local anesthetic delivery; however, catheter-based systems have several device- and technique-related limitations. In response, sustained-release local anesthetic formulations have been developed to extend analgesia after a single administration. These formulations include liposomal preparations, polymer-based delivery systems, and hydrogel-based carriers. Liposomal bupivacaine uses a multivesicular delivery system that acts as a local drug depot and gradually releases the anesthetic at the injection site. Polymer-based systems that combine local anesthetics with anti-inflammatory agents enhance analgesia by modulating the local tissue environment. Hydrogel-based carriers, including thermoresponsive and hyaluronic acid-based platforms, provide sustained drug release through three-dimensional polymer networks while minimizing systemic exposure. Recent advances in these delivery platforms have expanded the clinical potential of sustained-release local anesthetic technologies. Nevertheless, widespread clinical adoption remains constrained by several challenges, including burst release, variability in release kinetics, high costs, and limited clinical evidence. Sustained-release local anesthetic systems may provide catheter-free, prolonged postoperative analgesia in accordance with the principles of enhanced recovery after surgery. As drug delivery technologies continue to evolve, sustained-release local anesthetic formulations are likely to play an increasingly important role in perioperative pain management.