Development of Stimuli-Responsive Abuse-Deterrent Opioid Prodrugs
UC Los Angeles
Synthesis and Formulation
The rise in prescription opioid use and abuse throughout the United States over the past few decades has generated an epidemic that has caused over 100,000 deaths due to opioid overdose since 2016. The scale and complexity of this issue requires a multifaceted approach with many measures working in conjunction to effectively combat the crisis. To help resolve this epidemic, we have developed a dual-enzyme responsive peptide prodrug with a covalently attached opioid that is only cleaved in the presence of both enzymes. Work from our lab has demonstrated that these prodrugs can be altered to affect both abuse-deterrence and release rate, and the optimized prodrug sequence has been shown to demonstrate analgesic effects in vivo. Through this collaboration with the BioPACIFIC MIP facilities, we will effectively scale up this synthesis to gram scale to provide material for further analgesic studies to elucidate the prodrug’s effects on chronic and post-operative pain.