In vivo study of an extended release bupivacaine formulation following site-directed nerve injection

Site-directed administration of local anesthetic agents incorporated into a slow controlled-release injectable implant prolongs the analgesic effect. However, there are potential neuro- and myotoxic consequences. We evaluated a local anesthetic agent (bupivacaine) loaded into a slow-release biodegradable polymer based on castor oil and poly(lactic acid). The formulation was applied directly to the sciatic nerve area in female imprinting control region mice along with appropriate controls. Local nerve and muscle and systemic toxicity were evaluated over a 3-month period following injection of 0.05, 0.1, and 0.125-mL of the 15% bupivacaine-polymer formulation. Histological samples were prepared and examined; no signs of severe inflammation were observed. Histological inflammation signs were more prominent in both nerves and muscles following application of the largest volumes of the polymer formulation (0.1 and 0.125-mL). Following application of 0.1-mL, 15% bupivacaine-polymer formulation, maximal changes were seen in nerve samples two-days and two-weeks after injection, with complete resolution one-month following injection. Neither blank polymer nor plain bupivacaine 0.5% caused any histological changes. Local nerve and muscle toxicity were affected by duration the of exposure and dose of the local anesthetic agent. However, there were clear indications of time-related healing process 3-months after injection.