Antifungal Efficacy of a Thiazolyl Hydrazone Derivative Incorporated into a Self-Emulsifying Drug Delivery System in a Murine Model of Cryptococcosis

2-[2-(Cyclohexylmethylene)-hydrazinyl]-4-phenylthiazole (RN104) has shown notable antifungal activity against <i>Cryptococcus</i> species and low toxicity. This study aimed to assess the antifungal efficacy and survival benefits of RN104 incorporated into a self-emulsifying drug delivery system (SEDDS-RN104) compared to free RN104 and fluconazole (FCZ) in a murine model of <i>Cryptococcus neoformans</i> (H99) infection. The results demonstrated that SEDDS-RN104 significantly enhanced survival rates compared to free RN104 and FCZ, reducing the event rate (death) by 78% compared to FCZ. The mean survival time was 25 days in the SEDDS-RN104 group, compared to 14 days for free RN104 and 19 days for FCZ. Additionally, the fungal burden in the lungs was markedly reduced in the SEDDS-RN104 group, as confirmed by histopathological analysis. These findings suggest that SEDDS-RN104 effectively addresses the pharmacokinetic limitations of RN104, enhancing its antifungal efficacy and positioning it as a promising therapeutic alternative for cryptococcal infections.