A Novel Drug Delivery System for Controlled and Extended Release of Naloxone

Author

Hala Aldawod, University of the PacificFollow

Date of Award

2024

Document Type

Dissertation

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Pharmaceutical and Chemical Sciences

First Advisor

Mamoun Alhamadsheh

First Committee Member

Roshanak Rahimian

Second Committee Member

Miki S. Park

Third Committee Member

Qinliang Zhao

Fourth Committee Member

Melanie Felmlee

Abstract

The opioid crisis remains a severe public health challenge, exacerbated by the high incidence of overdose deaths associated with powerful synthetic opioids like fentanyl. Naloxone, an opioid antagonist, is a critical component in emergency responses to these overdoses due to its ability to rapidly reverse opioid effects. However, naloxone’s short duration of action limits its efficacy, particularly in environments with delayed medical follow-up. This dissertation presents a novel naloxone delivery system utilizing advanced prodrug technology to extend its therapeutic effects. The proposed system, based on a compound, AG10-Linker that enhances naloxone’s pharmacokinetic profile by modulating the solubility and absorption of a naloxone prodrug, thereby facilitating controlled and extended release of naloxone. This research investigates the synthesis, physicochemical properties, and in vivo efficacy of a naloxone prodrug formed by conjugating naloxone with AG10-Linker, demonstrating its potential to provide sustained protection against opioid toxicity. The findings suggest that this innovative approach could significantly impact clinical practice and the broader field of addiction medicine by improving outcomes in managing opioid overdoses.

Pages

122

Recommended Citation

Aldawod, Hala. (2024). A Novel Drug Delivery System for Controlled and Extended Release of Naloxone. University of the Pacific, Dissertation. https://scholarlycommons.pacific.edu/uop_etds/4281