Gold Nanoparticle-Encapsulated NS9283 for Prolonged Relief of Postoperative Neuropathic Pain

Postoperative neuropathic pain (PNP) is a common chronic condition that endures despite successful surgery and healing, substantially impacting patients' quality of life. This study investigates a novel gold nanoparticle-based drug delivery system, designed to enhance analgesics stability and efficacy for potential treatment of PNP via α4β2 nicotinic acetylcholine receptor activation. AuNPs were synthesized using a sodium citrate reduction method and conjugated with NS9283 through ligand exchange reactions. The physicochemical properties of the AuNPs-NS9283 complex were characterized using TEM and XPS. The efficacy of AuNPs-NS9283 was evaluated in a spared nerve injury (SNI) model in C57BL/6 mice. Mechanical pain thresholds were assessed using von-Frey filaments, and histological assessment was performed via hematoxylin-eosin staining. Intraperitoneal injection of low-dose α4β2 nAChR-selective positive allosteric modulator NS9283 provides rapid but short - term analgesia for neuropathic pain in mice. Loading NS9283 onto gold nanoparticles (AuNPs-NS9283) demonstrated superior stability and solubility, and targeted delivery prolongs the analgesic duration and achieves preliminary preemptive analgesia. HE staining revealed no significant nerve damage in any treatment group, indicating the safety of AuNPs-NS9283. AuNP-NS9283 represents a promising delivery strategy for prolonged relief of PNP. The study underscores the potential of nano-targeting technology in advancing PNP treatments.