Engineering Nanoscale Drug Delivery Systems for Pain.

Pain is a pervasive and multifaceted condition that imposes a significant medical and economic burden worldwide. This burden is underscored by the urgent need for transformative, non-addictive opioid alternatives. Nanomedicine offers a promising avenue for addressing the many limitations associated with conventional pain treatments, such as off-target effects, poor bioavailability, and rapid clearance, while enabling advanced therapeutic approaches such as precise spatiotemporal control and robust delivery of biologics. In this review, we explore the convergence of nanomedicine and pain management. We examine current literature on pain and chronic pain physiology and provide collated pharmacological data on current therapeutic approaches as a reference for formulation development. Recent advancements in lipid-based, polymeric, and inorganic nanoscale drug delivery systems (NDDS) for pain are surveyed, along with their progress toward clinical translation. Strategies for enhancing the efficacy of NDDS for pain are discussed, including supramolecular depot localization methods, active and passive targeting, controlled release kinetics, and the incorporation of stimuli-responsive elements for triggered release. We identify knowledge and technical gaps limiting progression beyond sustained-release formulations toward designs exploiting pain-specific biology. Overall, this review provides a comprehensive overview of the state-of-the-art in nanomedicine-based approaches for pain management and provides a roadmap for future innovations.