Microneedle patch-based transnasal delivery of naloxone

This study evaluates dissolving microneedle (MN) patches for naloxone (NAL) delivery via the transnasal route, addressing limitations seen with transdermal application of same and the limitations of conventional NAL intranasal sprays, which often require frequent redosing, particularly for long-acting opioids like fentanyl. MN patches composed of polyvinylpyrrolidone (PVP) and PVP/Chitosan were tested on porcine nasal mucosa. PVP patches achieved significantly higher 1-h cumulative permeation (7295.12 ± 2585.17 µg/cm²) compared to transdermal application (103 ± 15.18 µg/cm², p < 0.05). Over 24 h, cumulative permeation reached 13,113.20 ± 597.39 µg/cm² transnasally versus 4112.89 ± 773.40 µg/cm² transdermally (p < 0.05). Chitosan-PVP MN patches improved bioadhesion and demonstrated high 1-h cumulative permeation (3800.19 ± 940.51 µg/cm²). PVP MN patches with drug-loaded tips (MN/TO, where TO implies "tip only") delivered 933.90 ± 161.60 µg/cm² in 1 h that was also a remarkable increase over transdermal permeation (p < 0.05) but had lower 24 h permeation. Similar observation was seen with the PVP/Chitosan variant with drug loaded in just MN tips indicating that sustained delivery requires drug in both the tips and base. To further refine patch designs, a mathematical modeling framework was employed to simulate drug dissolution, permeation dynamics, and plasma concentration kinetics. Simulations demonstrated that optimized patches could achieve plasma profiles comparable to intranasal and intramuscular administration, while minimizing drug dose and patch size. Increasing drug concentration from 50 to 60 mg/ml decreased permeation, likely due to drug crystallization. Overall, MN patches showed consistent, sustained NAL delivery, providing an alternative option for efficient opioid overdose treatment.