Development and efficacy of tryptophol-containing emulgel for reducing subcutaneous fungal nodules from Scedosporium apiospermum eumycetoma
Thitinan Kitisin1, Watcharamat Muangkaew1, Sumate Ampawong2, Nichapa Sansurin3, Natthawut Thitipramote4, Passanesh Sukphopetch3
1 Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, 10400, Bangkok, Thailand., Thailand
2 Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University, 10400, Bangkok, Thailand., Thailand
3 Northeast Laboratory Animal Center, Khon Kaen University, 40002, Khon Kaen, Thailand., Thailand
4 Center of Excellence in Natural Products Innovation, Mae Fah Luang University, 57100, Chiang Rai, Thailand
Northeast Laboratory Animal Center, Khon Kaen University, 40002, Khon Kaen, Thailand.
Source of Support: None, Conflict of Interest: None
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.