Enhanced Antifungal Efficacy of Clove Oil using Nanosponges: A Novel Topical Delivery System

Clove oil (CO), derived from Syzygium aromaticum, is recognized for its broad-spectrum antimicrobial, antifungal, and anti-inflammatory properties. Still, its pharmaceutical uses are narrow due to poor aqueous solubility, chemical instability and potential skin irritation. This study aimed to enhance CO’s therapeutic efficacy using nanosponges as a novel delivery system. A 3² complete factorial design was used to optimise the synthesis of ethyl cellulose nanosponges, which were achieved utilising the emulsion solvent diffusion method. optimized formulation (F4) exhibited high entrapment efficiency (94.38%) and practical yield (93.23%). The nanosponge-loaded gel exhibited excellent physicochemical properties, including a pH of 5.4, viscosity of 13,092 cps, and sustained drug release (92.3% over 12 hours) following zero-order kinetics. In vivo studies in an immunosuppressed rat model of Candida albicans infection exhibited significantly improved antifungal efficacy with the nanosponges-loaded CO gel compared to pure CO gel. Histopathological analysis confirmed enhanced skin recovery, while the Draize patch test indicated no skin irritation. Stability studies further validated the formulation’s long-term integrity, with consistent drug release over 90 days. The results suggest that nanosponges-based CO delivery enhances antifungal activity, improves bioavailability, and minimizes skin irritation, making it a promising approach for topical antifungal therapy.