Abstract
Fungal pathogens in humans have now been increasingly reported worldwide. In addition, the most common pathogenic fungi that are resistant to standard antifungal agents, particularly azole group, are Candida albicans, Aspergillus fumigatus, and Scedosporium spp., causing the need to develop various antifungal drugs and pharmaceutical products to co-treat such infections. Several active antifungal compounds are obtained from medicinal plants and fungal metabolites known as fungal quorum-sensing molecules, which have been shown to inhibit the growth of another fungal species. One of the fungal quorum-sensing molecules is tryptophol. This study aimed to develop a topical product as tryptophol-containing emulgel for inhibiting the growth of Candida albicans, Aspergillus fumigatus, and Scedosporium species complex as Scedosporium apiospermum, which is the most reported cases of infections and deaths. The preliminary results showed the minimum inhibitory concentration (MIC) of tryptophol against three fungal species were 0.5, 1, and 2.5 mM, respectively, while the minimum fungicidal concentration (MFC) was 3, 6, and 6 mM, respectively. Tryptophol at the concentration of 6mM, which was the maximum inhibitory effect of the three fungal concentrations, was not found to induce toxicity in the fibroblast (HFF-1) cells and had no effect on the life cycle of the Caenorhabditis elegans worms. The results from the laboratory have led to the development of a prototype topical product as tryptophol-containing emulgel at a concentration of 6 mM. When examining the cosmeceutical properties, it was found that the properties were good according to the cosmeceutical standards. It is also stable in both accelerated testing and at room temperature. Tryptophol-containing emulgel was used to reduce the size of eumycetoma from S. apiospermum infection in rats with a significant reduction in the eumycetoma size after at least 14 days of treatment. Moreover, the prototype product had no stimulant effect in rats when tested histologically (40/40 animals), consistent with the results obtained in human volunteers, with no cream-induced irritation using closed patch test for 96 hours in 30/30 volunteers. The results showed that tryptophol-containing emulgel at a concentration of 6 mM was able to reduce the number of pathogenic fungi in humans Candida albicans and Aspergillus fumigatus (in vitro study), as well as to reduce eumycetoma size caused by S. apiospermum infections. Moreover, tryptophol-containing emulgel did not cause irritation in rats and in human volunteers. These laboratory results can be used as the basis knowledge for further application in clinical studies for the acquisition of co-treatments to treat mycoses or other skin pathogens.
