Comparing analgesic efficacy of microsphere-based and liposomal bupivacaine: a dose-response and time-dependent study in the spared nerve injury rat model

Liposomal bupivacaine has been shown to prolong anesthetic and analgesic effects compared with plain bupivacaine; however, its safety and clinical efficacy remain inconclusive in post-marketing surveillance. A novel microsphere-based formulation of bupivacaine, MBB, was developed to provide a stable release mechanism and favorable safety profile. This study aimed to compare the pharmacodynamic efficacy of the two extended-release formulations in relieving neuropathic pain. Twenty-four Sprague–Dawley rats underwent spared nerve injury (SNI). One week later, they were randomly assigned to receive Marcaine® (20 mg/kg), EXPAREL® (26.6 mg/kg), or MBB at low (30 mg/kg), medium (60 mg/kg), or high (90 mg/kg) doses injected into the sciatic nerve. Mechanical allodynia was assessed using ascending-force von Frey monofilaments before and at 2, 4, 8, 22, and 30 h after treatment. The maximum possible effect (%MPE) was calculated as (post-treatment − baseline)/(pre-treatment value − baseline) × 100. We found that low-dose MBB produced a comparable percentage of %MPE to EXPAREL® and Marcaine® control throughout the observation period. Medium- and high-dose MBB resulted in a more pronounced anti-allodynic effect than low-dose MBB and EXPAREL®, demonstrating a dose-dependent increase over time. Our study demonstrated that higher doses (60 and 90 mg/kg) of microsphere-based bupivacaine exhibited a more pronounced and longer-lasting anti-allodynic effect than the liposomal formulation in the rat spared nerve injury model.