Novel Electrospun Nanofiber Films for Treating Opioid Use Disorder

Author

Hadi Sudarjat, Virginia Commonwealth UniversityFollow

DOI

https://doi.org/10.25772/RPK0-T510

Author ORCID Identifier

https://orcid.org/0000-0003-1379-6135

Defense Date

2023

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Pharmaceutical Sciences

First Advisor

Dr. QIngguo Xu

Second Advisor

Dr. Matthew Halquist

Third Advisor

Dr. Charles O'Keefe

Fourth Advisor

Dr. Michael Hindle

Fifth Advisor

Dr. Matthew Banks

Abstract

OUD affects millions of people and induces a significant socio-economic burden. Since 1999, approximately 700,000 lives have been tragically lost, highlighting a profound public health challenge. With the increasing fatalities due to OUD, there is an urgent need for improved therapeutic strategies. Currently, methadone, buprenorphine, and naltrexone are the primary treatments for OUD. However, the daily regimen associated with methadone presents patient adherence challenges, emphasizing the demand for more patient-centric approaches. This study explored LAAM as alternative treatment for OUD, focusing its extended systemic half-life, suggesting potential for thrice-weekly dosing regimen. We invented a novel nanofiber buccal film for transmucosal LAAM delivery, aiming for improved bioavailability and efficacy over the conventional oral LAAM solution (ORLAAM^®). The LAAM-loaded nanofiber buccal film formulation is optimized to have immediate drug release, strong mucoadhesive strength, effective buccal mucosa penetration, and good storage stability at ambient conditions. The rabbit pharmacokinetic (PK) studies showed promising results, with the selected formulation (F5) exhibiting 3.5 times higher bioavailability over conventional oral LAAM solutions. Additionally, in vivo efficacy assessment demonstrated that LAAM nanofiber buccal films effectively reduced fentanyl choices in opioid-dependent rats with a thrice-weekly dosing regimen, paralleling the impact of daily methadone treatments. Our findings suggested the promising potential of LAAM-loaded nanofiber buccal films to treat OUD.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

12-11-2023