Tailoring Voriconazole Novasomes: Formulation, Characterization, Statistical Optimization, Ex-vivo Permeation, and Microbiological Revelations

Purpose Fungal infections remain a major concern due to rising incidence related to immunosuppression and chemotherapy, alongside growing antifungal resistance. Though Voriconazole (VCZ) displays robust potential against infections like aspergillosis and candidemia , its limited formulation availability highlights the need for alternative delivery approaches. Nanovesicle-based systems like novasomes (NV) have emerged as promising systems capable of enhancing delivery and overcoming current therapeutic limitations. Methods 2 3 factorial design was adopted to develop VCZ-loaded NV, with optimization based on entrapment efficiency (EE), vesicle size (VS), polydispersity index (PDI), and zeta potential (ZP), alongside evaluation of in-vitro release behavior, antifungal activity, Fourier transform infrared spectroscopy (FTIR), morphological characteristics, and stability of the optimized formula. The optimized formulation was incorporated into a Carbopol gel (DN1G) for ex vivo permeation studies. Results The formulation was optimized through a 2³ factorial design with EE%, VS, PDI, and ZP as critical responses, yielding the optimized VCZ-loaded NVs (DN1) with EE% (97.27±0.12 %), VS (256.93±4.40 nm), PDI (0.27±0.00), and ZP (-47.63±0.92 mV). In-vitro release studies confirmed controlled and sustained release. FTIR showed compatibility with the excipient, TEM analysis revealed spherical, non-aggregated vesicles, and stability evaluation revealed no significant alterations in selected parameters. DN1 demonstrated potent antifungal activity (MIC of 0.25 µg/mL) against C. albicans, and its incorporation into gel (DN1G) enhanced VCZ permeation by 1.89-fold. Conclusion This study highlights the potential of NV as a promising approach for VCZ, offering an effective alternative to conventional VCZ formulations, and encourages further exploration of vesicular systems for antifungal therapy.