Development and efficacy of tryptophol-containing emulgel for reducing subcutaneous fungal nodules from Scedosporium apiospermum eumycetoma

Thitinan Kitisin; Watcharamat Muangkaew; Sumate Ampawong; Nichapa Sansurin; Natthawut Thitipramote; Passanesh Sukphopetch

doi:10.4103/1735-5362.359437

Development and efficacy of tryptophol-containing emulgel for reducing subcutaneous fungal nodules from Scedosporium apiospermum eumycetoma

Res Pharm Sci. 2022 Oct 29;17(6):707-722. doi: 10.4103/1735-5362.359437. eCollection 2022 Dec.

Authors

Thitinan Kitisin¹, Watcharamat Muangkaew¹, Sumate Ampawong², Nichapa Sansurin³, Natthawut Thitipramote⁴, Passanesh Sukphopetch¹

Affiliations

¹ Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, 10400, Bangkok, Thailand.
² Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University, 10400, Bangkok, Thailand.
³ Northeast Laboratory Animal Center, Khon Kaen University, 40002, Khon Kaen, Thailand.
⁴ Center of Excellence in Natural Products Innovation, Mae Fah Luang University, 57100, Chiang Rai, Thailand.

Abstract

Background and purpose: Subcutaneous infections caused by Scedosporium apiospermum present as chronic eumycetomatous manifestations in both immunocompromised and immunocompetent individuals. Serious adverse effects/toxicities from the long-term use of antifungal drugs and antifungal resistance have been reported in patients with S. apiospermum infections. The present study aimed to determine the anti-S. apiospermum activities of fungal quorum sensing molecule known as tryptophol (TOH) and to develop a TOH-containing emulgel for treating S. apiospermum eumycetoma.

Experimental approach: Anti-S. apiospermum activities of TOH were determined and compared with voriconazole. Effects of TOH on S. apiospermum biofilm formation and human foreskin fibroblast (HFF)-1 cell cytotoxicity were determined. Moreover, TOH-containing emulgel was developed and physical properties, in vitro, and in vivo antifungal activities against S. apiospermum eumycetoma were evaluated.

Findings/results: The minimal concentration of TOH at 100 µM exhibited anti-S. apiospermum activities by reducing growth rate, germination rate, and biofilm formation with less cytotoxicity to HFF-1 cells than voriconazole. Further study on the development of an emulgel revealed that TOH-containing emulgel exhibited excellent physical properties including homogeneity, consistency, and stability. Treatment by TOH-containing emulgel significantly reduced subcutaneous mass in a mouse model of S. apiospermum eumycetoma. The histopathological assessment showed marked improvement after 14 days of TOH-containing emulgel treatment.

Conclusion and implications: TOH could be used as an anti-fungal agent against S. apiospermum infections. A novel and stable TOH-containing emulgel was developed with excellent anti-S. apiospermum activities suggesting the utilization of TOH-containing emulgel as an innovative therapeutic approach in the treatment of S. apiospermum eumycetoma.

Keywords: Emulgel; Eumycetoma; Quorum sensing molecule; Scedosporium apiospermum; Tryptophol..