The rapid emergence of resistance to classical antifungals has increased the interest in novel antifungal compounds. Curcumin and quercetin are two natural plant-derived bioactive molecules shown to promote wound healing in injured tissues. In this study, we investigated the in vitro susceptibility of several Aspergillus and Candida isolates to curcumin and quercetin encapsulated in nanovesicles with and without hyaluronan and elucidated the efficacy of these nanovesicles as topical drug delivery systems. Antifungal susceptibility testing performed according to the CLSI guidelines indicated that curcumin-quercetin co-encapsulated in nanovesicles without hyaluronan (CUR-QUE-NV-WH) had stronger activity against Candida isolates than fluconazole. Furthermore, CUR-QUE-NV-WH showed efficacy against fluconazole-resistant Candida isolates as evidenced by MICs at least two times lower than those of fluconazole. Examination of skin permeation profiles using an in vitro Franz diffusion cell system revealed that curcumin and quercetin delivered by nanovesicles were released and accumulated in the skin; however, only quercetin could penetrate through the skin layers. Collectively, our results demonstrate that CUR-QUE-NV-WH has potent antifungal activity against Candida isolates and might be a topical treatment, which warrants its further investigation as a novel antifungal agent. (C) 2020 Elsevier Masson SAS. All rights reserved.