Innovative Hybrid Microneedle Patch for Co-delivery of Varenicline and Melatonin: Development, Characterization, and Potential for Smoking Cessation.

OBJECTIVE: This study aimed to develop a microneedle patch loaded with varenicline and melatonin to improve patient compliance and enhance transdermal delivery for smoking cessation. SIGNIFICANCE: Smoking remains a major public health challenge. While varenicline is effective, oral administration can cause adverse effects, and vaccine-like approaches are limited by nicotine's small size. A painless, microneedle patch delivering varenicline together with melatonin could improve patient adherence and provide sustained delivery. METHODS: Microneedle arrays were fabricated using a blend of polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP), with Tween-80 added to enhance varenicline solubility. Comprehensive mechanical characterization, including nanoindentation, scratch testing, and atomic force microscopy, was performed. In vitro drug release and transdermal permeation studies were conducted, complemented by histological evaluation and fluorescence imaging. RESULTS: The microneedles exhibited high hardness, flexibility, and uniform surface topography, enabling effective skin penetration. In vitro studies showed cumulative transdermal permeation of 34.3% for varenicline and 41.6% for melatonin over 48 hours. The dual-drug-loaded microneedles demonstrated a sustained release profile. Histological analysis confirmed the creation of microchannels without damaging surrounding tissues. CONCLUSIONS: The combination of varenicline and melatonin in the microneedle shows promise in overcoming the limitations of current smoking cessation therapies, offering a patient-friendly and effective intervention. Future studies should include comparisons with commercial therapies and ex vivo dissolution studies (Q8).