ANTINOCICEPTION WITH A HYDROMORPHONE SUSTAINED RELEASE BIODEGRADABLE POLYMER DELIVERY SYSTEM (PLGA)

Abstract

S336 INTRODUCTION: Implantable delivery systems consisting of biodegradable materials are an alternative to injectable formulations or electronic pumps when chronic opioid or local anesthetic administration is necessary to treat pain [1,2] We present pilot pharmacological and efficacy results in the rat of a novel implantable biodegradable delivery system for hydromorphone(HM):poly(lactide-co-glycolide) (PLGA) matrix. MATERIAL AND METHODS: All procedures were approved by the Tufts Animal Research Committee. Male Sprague-Dawley rats (200-250 g) were implanted subcutaneously with PLGA matrices (rods) prepared to contain five doses of HM (0.5, 1.25, 3.13, 15, 30 mg) or placebo rods (PLGA only). An osmotic mini-pump (25 mg over 10 days) was used as a positive delivery control. Tail flick latency testing was used to determine percentage of maximal analgesic response (%MPR). Blood samples (0.3 ml) were collected prior to implantation, one hour later and every two days thereafter until the end of the study. Serum HM concentrations were determined by HPLC with EC detection. RESULTS: Release of hydromorphone at a steady rate release coupled with significant antinociception as compared to control was observed in the 15, 25 and 30 mg groups as compared to control up to 4 days (Fig). No local toxicity at the implantation site was observed. The decline of analgesia reflects the development of tolerance to the opioid, which is known to develop faster in pain models as compared to actual pain in patients. In summary our data suggest that the PLGA-HMh system may be a safe and cost-effective alternative to computerized or repeated or microprocessor controlled parenteral or enteral opioid administration when prolonged analgesia is required. Grant support by US Department of Defense DAMD17-96-C-6043 & the Saltonstall Fund.