Microneedle-mediated transdermal delivery of naloxone hydrochloride for treatment of opioid overdose

Naloxone (NAL) is administered parenterally or intranasally for treating opioid overdose. The short duration of action of NAL calls for frequent re-dosing which may be eliminated by the development of a transdermal system. This study aimed to assess the effect of microneedles on improving the skin permeation of NAL hydrochloride. In vitro permeation of NAL across intact and microneedle-treated (Dr. Pen (TM) Ultima A6) porcine skin was evaluated. The effect of microneedle length and application duration, and donor concentration on NAL permeation were investigated. In-vitro in-vivo correlation of the permeation results was done to predict the plasma concentration kinetics of NAL in patients. In vitro passive permeation of NAL after 6 h was observed to be 8.25+1.06 mu g/cm(2). A 56- and 37-fold enhancement was observed with 500 and 250 mu m needles applied for 1 min, respectively. Application of 500 mu m MNs for 2 min significantly reduced the lag time to similar to 8 min and increasing the donor concentration for the same treatment group doubled the permeation (p < 0.05). Modeling simulations demonstrated the attainment of pharmacokinetic profile of NAL comparable to those obtained with the FDA-approved intramuscular and intranasal devices. Microneedle-mediated transdermal delivery holds potential for rapid and sustained NAL delivery for opioid overdose treatment.

Automated summary

This study evaluated the effect of microneedles on improving the skin permeation of naloxone hydrochloride for the treatment of opioid overdose. The results showed that microneedles can significantly enhance the permeation of naloxone, with increased donor concentration and longer application duration leading to improved effects. Modeling simulations indicated that microneedle-mediated transdermal delivery could achieve a pharmacokinetic profile comparable to FDA-approved intramuscular and intranasal devices for naloxone administration in opioid overdose cases.