Engineering a microneedle patch for opioid overdose therapy

The opioid overdose epidemic, exacerbated by potent synthetic opioids such as fentanyl, presents a critical challenge to public health. Naloxone hydrochloride, a μ-opioid receptor antagonist, is the frontline therapeutic for overdose reversal; however, its clinical utility is constrained by rapid clearance, frequent re-dosing requirements, and complications associated with conventional delivery methods. In this work, we developed a minimally invasive microneedle (MN) patch system using gelatin methacryloyl (GelMA) hydrogels to enable sustained transdermal delivery of naloxone. Microneedle arrays (10×10, 600 µm height, 500 µm pitch) were fabricated with tunable UV crosslinking (0s, 15s, 30s, 60s) to optimize their physicochemical properties. Results indicated that 60s-crosslinked GelMA MNs exhibited enhanced mechanical strength, reduced enzymatic degradation (34.03% at 360 min), and a prolonged drug release profile (81.6% release over 24 h), verified via HPLC. Histological assessment in murine skin confirmed successful dermal penetration with crosslinked MNs. Furthermore, fluorescence imaging of fentanyl-treated HEK293T cells demonstrated functional naloxone antagonism, as evidenced by a time-dependent reduction in opioid-induced fluorescence. This study highlights GelMA-based microneedles as a robust and adaptable platform for opioid antagonist delivery. By modulating crosslinking parameters, the device achieves customizable release kinetics to counteract both immediate and long-duration overdose threats. This platform offers a promising alternative to injection-based therapies, with translational potential for point-of-care and community-level overdose management.

Name thesis:degree_name

Master of Science

Level thesis:degree_level

masters

Discipline thesis:degree_discipline

Biological Systems Engineering

Department dc:contributor.department

Biological Systems Engineering

Grantor dc:publisher

Virginia Tech

Year dc:date.issued

2025

Author dc:creator

• Tang, Yuze

Chair dc:contributor.committeechair

• Sun, Wujin

Committee members dc:contributor.committeemember

• Ali, Azahar
• Zhang, Chenming

• GelMA Microneedle
• Naloxone release

Statement dc:rights

• In Copyright

Licence dc:rights.uri

• http://rightsstatements.org/vocab/InC/1.0/

Language dc:language.iso

en

Dc Identifier Other

vt_gsexam:44271

OAI identifier oai:identifier

oai:vtechworks.lib.vt.edu:10919/135025