Innovative hybrid microneedle patch for co-delivery of varenicline and melatonin: development, characterization, and potential for smoking cessation.

Abstract

Smoking cessation remains a therapeutic challenge, and limitations associated with conventional oral varenicline therapy may affect patient adherence. This study aimed to develop and characterize a dissolving microneedle patch co-loaded with varenicline and melatonin for transdermal delivery. Microneedle arrays were fabricated using polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP), with Tween-80 incorporated to enhance the solubility of varenicline. The fabricated microneedles were evaluated for their mechanical and surface properties using nanoindentation, scratch testing, and atomic force microscopy. In vitro drug release and transdermal permeation studies were performed, while fluorescence imaging and histological analysis were used to assess microneedle insertion and skin integrity. The microneedles exhibited adequate hardness and flexibility, together with a uniform surface morphology, supporting effective penetration into the skin. Following 48 h of application, cumulative transdermal permeation of varenicline and melatonin reached 34.3% and 41.6%, respectively. The co-loaded microneedle formulation provided sustained release of both drugs over the study period. Histological evaluation confirmed the formation of discrete microchannels following microneedle insertion without significant disruption of the surrounding tissue. Overall, the findings demonstrate the feasibility of a varenicline-melatonin-loaded microneedle patch as a transdermal drug-delivery system for smoking cessation. Further investigation, including comparison with established commercial therapies and ex vivo dissolution and permeation studies, is warranted to establish its translational potential.