Background and Objective: Fluconazole (FLZ) is a novel triazole antifungistatic drug; topical administration of FLZ resulted in systemic absorption and skin inflammation, and thereby failed to achieve mycological eradication, resulting in low patient compliance and undermining therapy effectiveness. The aim of this study was to use the emulsion solvent evaporation technique to create FLZ-loaded nanosponges (NSs) using ethylcellulose (EC) and polyvinyl alcohol (PVA) as a stabiliser. Materials and Method: By varying the drug concentration (FLZ), EC, and PVA, four formulations were developed, each of which was then optimized through particle characterization (polydispersity index (PDI), scanning electron microscopy (SEM), zeta potential (ZP), drug entrapment, and loading efficiency). Results: SEM (Scanning Electron Microscope) analysis showed that the particle sizes of FLZ inclusion complexes ranged from 150 2 to 250 5 nm. The ZP was strong enough to produce stable formulations. FLZ was released from the nano sponges in a regulated manner for 24 hours in both in vitro and in vivo experiments. FTIR and DSC were used to validate the association of the FLZ with the nanosponges. The crystalline nature of FLZ was modified to an amorphous state due to the complexation with the nanosponges, according to an XRPD analysis. The FLZ nanosponges were found to be stable in a stability analysis. Conclusion: Therefore, ethyl cellulose-based nanosponges provide a novel method for controlling the release of FLZ for antifungal effects.