Development of Chronomers for narcotic antagonists.

Area of Science:

• Pharmacology and Drug Delivery Systems
• Biomaterials Science

Background:

• Development of long-acting injectable naltrexone formulations is crucial for opioid use disorder treatment.
• Existing naltrexone delivery methods require frequent administration, impacting patient adherence.

Purpose of the Study:

• To create a subcutaneous bioerodable naltrexone delivery system for sustained release over 1-6 months.
• To achieve constant and sufficient naltrexone release rates to block the euphoric effects of opioid drugs.

Main Methods:

• Naltrexone was uniformly dispersed within a solid, hydrophilic CHRONOMER matrix designed for predictable surface erosion.
• In vitro kinetic studies were performed to optimize system composition.
• In vivo efficacy was assessed using the tail-flick test in rats to measure naltrexone's antagonism of morphine analgesia.

Main Results:

• Intravenous naltrexone at 4 and 16 ug/kg/hr achieved 54% and 89% antagonism of morphine analgesia, respectively.
• Toxicological studies indicated no adverse effects from CHRONOMER materials or their hydrolysis products.
• Preliminary sterilization studies confirmed no adverse effects on CHRONOMER/naltrexone systems after 2.5 or 5.0 mrads of 60Co irradiation.

Conclusions:

• The developed bioerodable naltrexone-CHRONOMER system demonstrates potential for sustained subcutaneous delivery.
• The system effectively antagonizes opioid effects, suggesting promise for managing opioid dependence.
• CHRONOMER appears to be a safe and effective matrix for long-term naltrexone delivery.