Degree Name
PhD (Doctor of Philosophy)
Program
Biomedical Sciences
Date of Award
12-2024
Committee Chair or Co-Chairs
Ashana Puri
Committee Members
Stacy Brown, Siva Digavalli, Brooke Schmeichel, Daniel Connors
Abstract
Opioid overdose crisis continues to demand innovative solutions for rapid and effective drug administration. Naloxone (NAL), a critical opioid antagonist, has been the primary treatment for reversing opioid-induced respiratory depression. However, its current delivery methods, such as intravenous and intranasal formulations, are limited by their invasive nature, short half-life, and the need for repeated dosing. This dissertation investigates advanced drug delivery technologies aimed at overcoming these challenges and enhancing the clinical utility of NAL.
This research focused on improving the transdermal and transnasal delivery of NAL using minimally invasive techniques. Various approaches were evaluated, including sonophoresis, microneedles, laser ablation, dermaplaning and microdermabrasion, all of which demonstrated significant potential to enhance drug permeation through the skin. These methods shortened the lag time for drug delivery and provided sustained-release profiles, addressing key limitations of existing NAL delivery forms. Among the techniques explored, microneedles (MNs) showed exceptional promise in being advanced to enable both rapid and sustained drug release. Polyvinylpyrrolidone-based dissolving MN prototypes of varying geometries were developed and evaluated in this study with attributes pertinent to significant skin delivery. Findings showed the impact of MN density and geometry on NAL delivery from these patches. Pharmacokinetic predictions revealed optimal designs to meet clinical needs. Further optimization was achieved by integrating iontophoresis with dissolvable microneedles, enhancing the controlled and targeted delivery of NAL. This combination approach resulted in improved drug flux, and the potential to minimize the need for frequent dosing during overdose emergencies. Additionally, the transnasal application of the developed patch provides another non-invasive alternative for fast-acting NAL administration, which could expand access to overdose treatments by first responders and laypersons.
This work highlights the potential of these advanced drug delivery systems to not only improve the bioavailability of NAL, but also to offer more patient-friendly, accessible, and effective solutions for opioid overdose treatment. The findings suggest that these technologies could play a pivotal role in addressing the limitations of current NAL delivery methods, ultimately enhancing patient outcomes and public health efforts in combating the opioid crisis.
Document Type
Dissertation - embargo
Recommended Citation
Tijani, Akeemat O., "Overcoming the Barrier to the Clinical Application of Naloxone: Application of Drug Delivery Technologies" (2024). Electronic Theses and Dissertations. Paper 4482. https://dc.etsu.edu/etd/4482
Copyright
Copyright by the authors.