Voriconazole Loaded Spanlastics: Design, Formulation, Optimization, and Randomized Controlled Clinical Insights for Vulvovaginal Candidiasis Therapy

Abstract

Voriconazole, a potent antifungal agent, has emerged as a promising candidate for managing vulvovaginal candidiasis. The market availability of voriconazole as tablets or injections, along with potential side effects, highlights the need for a successful alternative delivery system. Through comprehensive experimental design, voriconazole-loaded spanlastics were developed using a 3 2 -factorial design. The optimized system based on factorial outcomes exhibited desirable characteristics in terms of entrapment efficiency (74.31 ± 0.39%), vesicle size (246.4 ± 2.2 nm), polydispersibility index (0.369 ± 0.01), & zeta potential (-37.5 ± 0.17 mV). Further characterization for the optimized system was performed in terms of transmission electron microscopy, Fourier transform infrared spectroscopy, and in-vitro antifungal assessment, where the latter showcased the potent effectiveness of voriconazole against various Candida species. Moreover, the integration of the optimized voriconazole-loaded spanlastic system into a gel was implemented for the assessment of ex-vivo permeation through the vaginal mucosa of rats, where the optimized system gel revealed a remarkable 1.3-fold enhancement in permeation relevant to the control VCZ gel. Notably, the clinical performance of optimized system gel was involved in a randomized controlled study for assessment of safety and efficacy in comparison to a market product (Canesten ® 2% clotrimazole). Clinical evaluation revealed that the optimized VCZ-loaded SP gel and the market product, Canesten. (2% clotrimazole) exhibited comparable efficacy in terms of clinical satisfaction, side effects, and time to clinical cure from VVC. These findings highlight the potential of the optimized system as a promising approach for improved treatment outcomes in women with vaginal candidiasis with no adverse effects. Graphical Abstract

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