Bupivacaine-Loaded PLGA Nanoparticles for Long-Term Management of Chronic Neuropathic Pain

Background/Objectives: Chronic neuropathic pain imposes a substantial burden on patients and society, and opioids are unsuitable for long-term use due to their addictive potential. To overcome this limitation, we encapsulated bupivacaine in PLGA nanoparticles to achieve sustained-release analgesia with reduced systemic toxicity. Methods: The analgesic efficacy was evaluated in rat models of chronic compression of the dorsal root ganglion (CCD) and chronic constriction injury (CCI). Nanoparticles were characterized using scanning electron microscopy (SEM) for morphology and size, and X-ray diffraction (XRD) for dispersion. In vivo electrophysiological recordings, including action potentials from DRG neuronal somata and compound action potentials in the sciatic nerve, were performed to investigate peripheral analgesic mechanisms, while plasma bupivacaine concentrations were measured by high-performance liquid chromatography (HPLC). Results: Bupivacaine nanoparticles significantly alleviated mechanical pain in both CCD and CCI rats, but had no effect on thermal pain. They selectively inhibited C-fiber conduction without affecting A-fibers. Importantly, plasma bupivacaine levels remained well below the corresponding toxic thresholds, indicating a favorable safety profile. Conclusions: These findings suggest that bupivacaine-loaded PLGA nanoparticles represent a promising long-term therapeutic option for chronic neuropathic pain management.