Engineering a microneedle patch for opioid overdose therapy

Abstract

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.