Fabrication and characterization of voriconazole-loaded dissolving microneedle systems: a synergistic approach combining 3D printing and vacuum compression molding.

Deep fungal skin infections remain challenging to treat due to the limited penetration of conventional topical formulations and systemic adverse effects associated with oral antifungal therapy. In this study, voriconazole (VRC)-loaded dissolving microneedle (DMN) systems were developed using an integrated manufacturing approach combining liquid crystal display (LCD)-based three-dimensional (3D) printing, polydimethylsiloxane (PDMS) molding, and vacuum compression molding (VCM). Cone-shaped, 3D-printed microneedle (MN) templates were used to produce Soluplus®-based DMN systems containing 1% (w/w) VRC. Following optimization of VCM parameters, the fabricated DMN systems closely replicated the master geometry and enabled effective insertion into Parafilm® M and full-thickness human skin. Physicochemical analyses confirmed formulation stability under the applied processing conditions. Complete needle dissolution occurred within 12.5 min, and in vitro studies further revealed rapid VRC release from the needle compartment (30-45 min), followed by sustained release from the base. Ex vivo studies demonstrated predominantly epidermal VRC deposition for both the DMN systems and the suspension gel, with no detectable transdermal permeation. Moreover, significantly higher dermal deposition was observed following application of the DMN systems. The DMN systems exhibited antifungal activity against Candida albicans, including a fluconazole-resistant strain. Microtox® screening indicated low bioluminescence inhibition for VRC-loaded DMN systems, with the reduction in luminescence predominantly associated with the Soluplus® matrix rather than the incorporated drug. Collectively, these findings suggest that Soluplus®-based DMN systems may represent a promising platform for localized VRC delivery in deep fungal skin infections.