Advanced Hydrogel Systems for Local Anesthetic Delivery: Toward Prolonged and Targeted Pain Relief.

Local anesthetics (LAs) have been indispensable in clinical pain management, yet their limitations, such as short duration of action and systemic toxicity, necessitate improved delivery strategies. Hydrogels, with their biocompatibility, tunable properties, and ability to modulate drug release, have been extensively explored as platforms for enhancing LA efficacy and safety. This narrative review explores the historical development of LAs, their physicochemical properties, and clinical applications, providing a foundation for understanding the integration of hydrogels in anesthetic delivery. Advances in thermoresponsive, stimuli-responsive, and multifunctional hydrogels have demonstrated significant potential in prolonging analgesia and reducing systemic exposure in preclinical studies, while early clinical findings highlight the feasibility of thermoresponsive hydrogel formulations. Despite these advancements, challenges such as burst release, mechanical instability, and regulatory considerations remain critical barriers to clinical translation. Emerging innovations, including nanocomposite hydrogels, biofunctionalized matrices, and smart materials, offer potential solutions to these limitations. Future research should focus on optimizing hydrogel formulations, expanding clinical validation, and integrating advanced fabrication technologies such as 3D printing and artificial intelligence-driven design to enhance personalized pain management. By bridging materials science and anesthetic pharmacology, this review provides a comprehensive perspective on current trends and future directions in hydrogel-based LA delivery systems.