Local Delivery of Non-opioid Analgesic Microparticles to Modulate Post-surgical Pain

Postsurgical pain (PSP) is a common complication in surgical patients that can progress to chronic pain and opioid dependence. Current analgesics, including opioids and non-opioid agents, are limited by short durations of action and adverse effects. This study reports the development and evaluation of extended-release bupivacaine microparticles (BuMPs) designed to provide sustained local analgesia and improve post-surgical pain management.

BuMPs were fabricated using PLGA and tested in a mouse sciatic nerve injury (SNI) model, a clinically relevant model of neuropathic pain. Mice received a single local injection of BuMPs or blank microparticles. Mechanical hypersensitivity was assessed using the von Frey test over a 21-day period. BuMPs were also compared to an FDA-approved liposomal bupivacaine formulation.

We fabricated BuMPs by the hydrogel template method and confirmed their uniform size distribution. Thus prepared BuMPs exhibited extended bupivacaine release in vitro and in vivo in a healthy rat model. In a SNI model, BuMP-treated mice exhibited significantly reduced mechanical hypersensitivity compared to controls, with analgesic effects sustained for up to 21 days. BuMPs provided prolonged pain relief, demonstrating effective modulation of postsurgical and neuropathic pain.

BuMPs offer a promising non-opioid strategy for long-acting PSP management. Their extended analgesic effect from a single perioperative injection may reduce opioid reliance, improve patient recovery, and serve as a complementary therapy.