Formulation, development and in vivo characterization of tioconazole PLGA microparticles loaded microneedle array patches for fungal infection as long-acting transdermal delivery

Background Fungal infections affect over 500 million people annually, with bacterial vaginosis accounting for 29%. Candida recurrence occurs in 9% of women, and azole resistance is rising, while biofilms and pH imbalance hinder therapy. This study developed tioconazole (TCZ)-loaded PLGA microparticles integrated into a microneedle array patch (MAP) for sustained transdermal delivery against fungal infections. Methods TCZ-PLGA microparticles were optimized using Box–Behnken design and characterized for size, PDI, entrapment efficiency, and zeta potential, with XRD, DSC, and SEM analyses. The optimized formulation was integrated into a MAP, followed by ex vivo diffusion, in vitro release, skin irritation, and pharmacokinetic evaluations. Results The optimized formulation (Batch B9) exhibited a particle size of 516.11 ± 1.15 nm, a narrow size distribution of 0.272 ± 0.18, a high entrapment efficiency of （81.60 ± 0.52）%, and a zeta potential of （−7.4 ± 0.23）mV. Additionally, the amorphous transformation of TCZ within the PLGA carrier was disclosed by XRD and DSC studies. SEM analysis revealed that TCZ-PLGA particles exhibited a circular shape. The TCZ-PLGA microparticle-integrated MAP demonstrated no evidence of irritation to the skin in rats. It enhanced drug diffusion ex vivo (1.85-fold compared to pure tioconazole-loaded MAP) and achieved 90% drug release within 12 h. Pharmacokinetic analysis showed that the TCZ-PLGA microparticle-integrated MAP had a half-life of (3.0 ± 0.59) h and an AUC 0-t of 33.30 ± 1.54 μg/mL·h, indicating a steady and controlled release profile. In contrast, pure tioconazole exhibited a short half. Conclusion The TCZ-PLGA MAP significantly improved drug retention and bioavailability, offering a safe, long-acting strategy with enhanced therapeutic efficacy and patient compliance for fungal infection treatment.