Abstract
Transdermal drug delivery is limited by the barrier function of the stratum corneum, which restricts the permeation of large, poorly water-soluble molecules. Dissolving microneedles (DMNs) overcome this barrier by physically breaching the stratum corneum and releasing therapeutics directly into the viable epidermis and dermis, while nanoemulsion (NE) carriers improve the solubility and skin penetration of lipophilic drugs. In the present study, Amphotericin B (AmB) a high-molecular-weight, poorly soluble and poorly bioavailable antifungal agent — was used as a model drug to develop and characterize a nanoemulsion-loaded dissolving microneedle (AmB-NE-DMN) system. Solubility screening identified Capmul MCM C-8 EP/NF and Tween 80 as the optimal oil and surfactant components. Five AmB-NE formulations (F1–F5) were prepared by SpeedMixer-assisted probe sonication using varying polyvinyl alcohol (PVA)–polyvinyl pyrrolidone (PVP) ratios and cast into silicone moulds (600 needles/0.75 cm²) by a single-step centrifugation method. The optimized formulation, AmB-NE-F5, produced monodisperse droplets of 296.65 ± 4.74 nm (polydispersity index 0.192 ± 0.011; zeta potential −24.90 ± 1.05 mV) and remained physically stable over 15 days of storage at 4°C and 25°C. AmB-NE-DMN-F5 arrays showed excellent mechanical strength (1.4% height reduction under 32 N compression) and penetrated to the fourth Parafilm M® layer (~508 μm). Ex vivo permeation and in vitro antifungal testing against Candida albicans demonstrated markedly higher AmB permeation than microneedle-free patches and a superior zone of inhibition (68.75 ± 4.79 mm) compared with conventional AmB discs, with additional synergistic antifungal activity contributed by the Capmul MCM C-8 oil phase. These findings support the AmB-NE-DMN platform as a promising strategy for transdermal and intradermal antifungal therapy.