Formulation and Evaluation of Cyclodextrin-Based Nanosponge Gel for Topical Delivery of Voriconazole

Voriconazole is a highly potent, broad-spectrum triazole antifungal agent effective against severe superficial and systemic fungal infections; however, its clinical utility for topical administration is severely restricted by its poor aqueous solubility, chemical instability, and semi-polar character. To overcome these limitations, this study aimed to engineer cyclodextrin-based nanosponges (CD-NS) using β-cyclodextrin and 2-hydroxypropyl-β-cyclodextrin cross-linked with diphenyl carbonate (DPC) for the efficient encapsulation of voriconazole. The drug was successfully loaded into the optimized nanosponges using a freeze-drying technique, yielding nanometric particles with a narrow polydispersity index, high negative zeta potential, and complete drug amorphization as confirmed by FTIR, DSC, and XRPD analyses. These optimized nanosponge complexes were subsequently incorporated into a 1% w/w Carbopol 934 hydrogel enriched with permeation enhancers. In-vitro release studies of the hydrogel demonstrated a biphasic profile characterized by an initial burst followed by sustained drug release. Furthermore, ex-vivo and in-vivo skin permeation studies revealed that the nanosponge-loaded hydrogel significantly enhanced the localized deposition of voriconazole in the stratum corneum and epidermis-dermis layers without facilitating systemic transdermal transport. Coupled with superior in-vitro antifungal activity against Candida albicans and Aspergillus fumigatus, this cyclodextrin-based nanosponge hydrogel presents a highly effective, targeted, and stable topical delivery system for the treatment of cutaneous fungal infections.