Dual mucoadhesive nanoparticle-hydrogel platform for sustained intravaginal miconazole delivery with anti-biofilm activity against vulvovaginal candidiasis.

Vulvovaginal candidiasis (VVC), primarily caused by Candida albicans, remains a global health concern, and conventional therapies struggle to maintain effective drug concentrations at the infection site. Miconazole (MIC)-loaded polymeric nanoparticles (MIC-PNPs) were prepared by nanoprecipitation, and Eudragit E 100 concentration, polyvinyl alcohol concentration, and organic-to-aqueous phase ratio were optimized using Design Expert® software. The optimized nanoparticles showed nanometric size, high zeta potential, and excellent entrapment efficiency. Fourier-transform infrared spectroscopy confirmed component compatibility, X-ray diffraction and differential scanning calorimetry indicated conversion of MIC to an amorphous state, and scanning electron microscopy revealed spherical morphology. MIC-PNPs were incorporated into a Carbopol-934 hydrogel (MIC-PNPG), which was characterized for physical properties, drug content, spreadability, mucoadhesive strength, and viscosity. MIC-PNPs and MIC-PNPG released 68% and 58% of MIC, respectively, over 24 h at pH 4.2, following Korsmeyer-Peppas kinetics. MIC-PNPG showed substantial ex vivo mucoadhesive strength. Antifungal assays confirmed superior activity of MIC-PNPs over free MIC, and antibiofilm studies showed concentration-dependent inhibition and degradation of C. albicans biofilms, with MIC-PNPG outperforming MIC-PNPs and free MIC. The hen's egg test-chorioallantoic membrane assay showed significantly lower irritation for nanoparticle-based formulations than the marketed product. Ex vivo studies demonstrated enhanced drug permeation and vaginal tissue retention of MIC-PNPs. In vivo, treatment significantly reduced infection pathogenicity, supported by histopathological findings. These results suggest MIC-PNPs as a promising candidate warranting further clinical investigation for VVC treatment.