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

**Authors:** Iara R. Silva, Victor A. T. Leocádio, Gustavo J. C. Freitas, Renata B. Oliveira, Elaine A. Leite, Daniel A. Santos, Isabela C. César

PMC · DOI: 10.1021/acsomega.5c02705 · ACS Omega · 2025-06-21

## TL;DR

A new drug delivery system improved the effectiveness of an antifungal compound in treating cryptococcosis in mice.

## Contribution

A self-emulsifying drug delivery system significantly enhanced the antifungal efficacy of RN104 in a murine model.

## Key findings

- SEDDS-RN104 reduced the death event rate by 78% compared to fluconazole.
- The mean survival time was 25 days with SEDDS-RN104 versus 14 days with free RN104.
- Fungal burden in the lungs was significantly reduced in the SEDDS-RN104 group.

## Abstract

2-[2-(Cyclohexylmethylene)­hydrazinyl]-4-phenylthiazole
(RN104)
has shown notable antifungal activity against Cryptococcus 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 Cryptococcus neoformans (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.

## Linked entities

- **Chemicals:** fluconazole (PubChem CID 3365)
- **Diseases:** cryptococcosis (MONDO:0005724)
- **Species:** Cryptococcus neoformans (taxon 5207)

## Full-text entities

- **Diseases:** infection (MESH:D007239), death (MESH:D003643), toxicity (MESH:D064420), fungal (MESH:D009181), Cryptococcosis (MESH:D003453), cryptococcal infections (MESH:D016919)
- **Chemicals:** FCZ (MESH:D015725), 2-[2-(Cyclohexylmethylene)-hydrazinyl]-4-phenylthiazole (-)
- **Species:** Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12223863/full.md

## References

18 references — full list in the complete paper: https://tomesphere.com/paper/PMC12223863/full.md

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Source: https://tomesphere.com/paper/PMC12223863