NAL's hydrophilicity and the inherent lipophilic properties of the stratum corneum hinders its capacity for immediate delivery through skin in opioid rescue cases. In this study, we had sought to investigate the feasibility of using minimally invasive physical ablative techniques including sonophoresis, laser, dermaplaning, microneedles, and microdermabrasion for systemically delivering NAL via the skin. These techniques reduced lag time to NAL delivery to about 3-12 min from 71.22 ± 9.62 min seen for passive delivery. Also, they all significantly enhanced the amount of NAL delivered in 1 h and over 24 h period of evaluation as compared to the passive group (p < 0.05). Sonophoresis and laser showed the greatest delivery in 1 h, followed by dermaplaning. The cumulative amount of drug delivered by these approaches in 1 h were 1277.95 ± 387.06, 83.33 ± 11.11, 30.66 ± 5.67 µg/cm2, respectively. Though the most remarkable, inconsistencies in in vitro permeation profile of NAL were observed with the 1 MHz ultrasound frequency used. With proper optimization of the conditions of use and design, the different approaches explored in this study can be potentially applied for the systemic delivery of naloxone in opioid overdose emergencies and opioid disaccustoming purposes.
Keywords: Ablation; Laser; Microdermabrasion; Microneedles; Sonophoresis; Transdermal delivery.
Copyright © 2023 Elsevier B.V. All rights reserved.