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含色醇乳胶凝胶用于减少足菌肿皮下真菌结节的研发与疗效

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

作者信息

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

机构信息

Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, 10400, Bangkok, Thailand.

Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University, 10400, Bangkok, Thailand.

出版信息

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

DOI:10.4103/1735-5362.359437
PMID:36704435
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9872179/
Abstract

BACKGROUND AND PURPOSE

Subcutaneous infections caused by 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 infections. The present study aimed to determine the anti- activities of fungal quorum sensing molecule known as tryptophol (TOH) and to develop a TOH-containing emulgel for treating eumycetoma.

EXPERIMENTAL APPROACH

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

FINDINGS/RESULTS: The minimal concentration of TOH at 100 µM exhibited anti- 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 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 infections. A novel and stable TOH-containing emulgel was developed with excellent anti- activities suggesting the utilization of TOH-containing emulgel as an innovative therapeutic approach in the treatment of eumycetoma.

摘要

背景与目的

由[具体真菌名称未给出]引起的皮下感染在免疫功能低下和免疫功能正常的个体中均表现为慢性真菌性足菌肿。长期使用抗真菌药物的严重不良反应/毒性以及真菌感染患者的抗真菌耐药性已有报道。本研究旨在确定被称为色醇（TOH）的真菌群体感应分子的抗[真菌名称未给出]活性，并开发一种含TOH的乳胶凝胶用于治疗[真菌名称未给出]性足菌肿。

实验方法

测定TOH的抗[真菌名称未给出]活性并与伏立康唑进行比较。确定TOH对[真菌名称未给出]生物膜形成和人包皮成纤维细胞（HFF）-1细胞毒性的影响。此外，开发了含TOH的乳胶凝胶并评估其物理性质、[此处原文缺失部分内容]以及对[真菌名称未给出]性足菌肿的抗真菌活性。

研究结果

100μM的TOH最低浓度通过降低生长速率、发芽率和生物膜形成表现出抗[真菌名称未给出]活性，对HFF-1细胞的细胞毒性低于伏立康唑。对乳胶凝胶开发的进一步研究表明，含TOH的乳胶凝胶表现出优异的物理性质，包括均匀性、稠度和稳定性。含TOH的乳胶凝胶治疗显著减轻了[真菌名称未给出]性足菌肿小鼠模型中的皮下肿块。组织病理学评估显示，含TOH的乳胶凝胶治疗14天后有明显改善。

结论与意义

TOH可作为抗[真菌名称未给出]感染的抗真菌剂。开发了一种新型且稳定的含TOH乳胶凝胶，具有优异的抗[真菌名称未给出]活性，表明含TOH乳胶凝胶可作为治疗[真菌名称未给出]性足菌肿的创新治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e88/9872179/9b6e876d6295/RPS-17-707-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e88/9872179/59ca850a4958/RPS-17-707-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e88/9872179/217f7bc16d94/RPS-17-707-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e88/9872179/1d66d36c8149/RPS-17-707-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e88/9872179/9b6e876d6295/RPS-17-707-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e88/9872179/59ca850a4958/RPS-17-707-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e88/9872179/217f7bc16d94/RPS-17-707-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e88/9872179/1d66d36c8149/RPS-17-707-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e88/9872179/9b6e876d6295/RPS-17-707-g007.jpg

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