Fungal infections represent a significant challenge in human medicine. With increasing resistance to conventional antifungal therapies and the recurrent nature of these infections, the need for more effective treatment options is critical. One promising avenue of research involves selenium sulfide, a compound with well-established antifungal properties, which has been used historically in various antifungal formulations. Recent advancements in in vitro studies have revealed new insights into selenium sulfide's potential as an antifungal treatment, particularly for infections caused by Malassezia species [1]. This white paper explores these advancements and the implications for future therapeutic developments. Importance of Antifungal Treatments Fungal infections, especially those caused by Malassezia species, particularly affect the human population. Malassezia is implicated in a range of conditions, including dandruff, seborrheic dermatitis, and superficial fungal infections in cats and dogs. [2] The challenge with current antifungal treatments is their often-limited efficacy and the increasing emergence of systemic infections. Oral and topical therapies can sometimes yield unsatisfactory outcomes, and recurrence is common. The absence of standardized treatment protocols further complicates the management of these infections.[3] Therefore, it is essential to explore new strategies and compounds to address these challenges more effectively. Overview of Selenium Sulfide Selenium sulfide (SeS2) is a compound with broad antifungal activity, particularly against Malassezia species, a group of lipid-dependent fungi. [4] [5]. Its mechanisms of action include both antifungal and keratolytic effects, making it useful not only for combating infections but also for addressing the excess keratin production seen in conditions like dandruff and seborrheic dermatitis. [6] Historically, selenium sulfide has been used in shampoos and topical applications, demonstrating good efficacy against fungal infections on the scalp and skin. Recent In vitro studies have extended the understanding of selenium sulfide's role in antifungal therapy, opening the door to new potential applications. [6] In vitro Studies on Selenium Sulfide Several studies have focused on the In vitro antifungal efficacy of selenium sulfide and related compounds, with promising results that could shape future clinical treatments. 1. Selenium Nanoparticles in Antifungal Treatment Another promising area of research involves the use of selenium nanoparticles (SeNPs) synthesized through myconanotechnology. This approach leverages the antifungal properties of selenium in a nanoparticle form, enhancing its efficacy. In vitro studies demonstrated that SeNPs significantly inhibited fungal growth across several phytopathogens, including Pyricularia grisea and Alternaria solani. The concentration-dependent inhibition observed in these trials underscores the potential of SeNPs as eco-friendly and highly effective antifungal agents. These findings could inform the development of sustainable agricultural and medical antifungal treatments.[7] 2. Comparison of Selenium Nanoparticles and Selenium Disulfide A comparative study investigated the antifungal efficacy of selenium nanoparticles (SeNPs) and selenium disulfide (SeS2) against two species of Malassezia—M. sympodialis and M. furfur. SeNPs showed a much lower minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) compared to SeS2, indicating their superior potency. For example, the MIC for SeNPs against M. furfur was 50 µg/ml, whereas it was 150 µg/ml for SeS2. These findings suggest that selenium nanoparticles could offer a more potent alternative to selenium sulfide in treating Malassezia infections. However, the absence of a post-antifungal effect (PAFE) in both SeNPs and SeS2 indicates that long-term exposure may be necessary to prevent fungal regrowth, pointing to the need for well-considered treatment regimens. [8] Cytotoxicity and Safety Profile of Selenium Sulfide In vitro studies have also investigated the cytotoxicity of selenium sulfide on mammalian cells, which is critical for determining its safety in clinical use. Selenium sulfide demonstrated minimal cytotoxic effects on human dermal fibroblasts at concentrations effective for antifungal activity. Studies comparing selenium sulfide with other antifungal agents, such as zinc pyrithione and ketoconazole, found that selenium sulfide exhibited strong keratolytic properties with an acceptable safety profile.[9] These results suggest that selenium sulfide can be used safely in topical formulations for human and animal applications without significant risk of cytotoxicity, reinforcing its clinical potential. [10] Future Directions and Clinical Implications While In vitro studies provide valuable insights into the antifungal potential of selenium sulfide and its nanoparticle counterparts. The development of selenium-based formulations, including nanoparticles, also presents exciting opportunities for eco-friendly and sustainable antifungal treatments. [11] These advancements could have far-reaching implications for human medicine. In conclusion, advancements in antifungal treatments, particularly those involving selenium sulfide and selenium nanoparticles, offer promising avenues for combating fungal infections. In vitro studies have demonstrated the potent antifungal activity of selenium compounds, especially against Malassezia species. These findings highlight selenium sulfide's potential as an effective and safe treatment for fungal infections in both human and veterinary medicine. With continued exploration, selenium-based antifungal therapies could play a pivotal role in addressing the challenges of recurrent and resistant fungal infections. IND2363534 04 AUG 2025 For the use of a Registered Medical Practitioner or a Hospital or a Laboratory only 1. [1] A. J. Carrillo-Mu~ Noz et al., “In vitro antifungal activity of topical and systemic antifungal drugs against Malassezia species,” 2013, doi: 10.1111/myc.12076. [2] S. Hobi, C. Cafarchia, V. Romano, and V. R. Barrs, “Malassezia: Zoonotic Implications, Parallels and Differences in Colonization and Disease in Humans and Animals,” J Fungi (Basel), vol. 8, no. 7, Jul. 2022, doi: 10.3390/JOF8070708. [3] V. T. Andriole, “Current and future antifungal therapy: new targets for antifungal therapy,” Int J Antimicrob Agents, vol. 16, no. 3, pp. 317–321, 2000, doi: 10.1016/S0924-8579(00)00258-2. [4] O. Długosz et al., “Antimicrobial and antiviral activity of selenium sulphide nanoparticles synthesised in extracts from spices in natural deep eutectic solvents (NDES),” Sustainable Materials and Technologies, vol. 32, p. e00433, Jul. 2022, doi: 10.1016/J.SUSMAT.2022.E00433. [5] M. Billamboz and S. Jawhara, “Anti-Malassezia Drug Candidates Based on Virulence Factors of Malassezia-Associated Diseases,” Microorganisms, vol. 11, no. 10, Oct. 2023, doi: 10.3390/MICROORGANISMS11102599. [6] A. K. Gupta, R. R. Mays, and K. A. Foley, “Topical Antifungal Agents,” Comprehensive Dermatologic Drug Therapy, Fourth Edition, pp. 480-492.e5, Jan. 2020, doi: 10.1016/B978-0-323-61211-1.00042-5. [7] S. M. Joshi, S. De Britto, S. Jogaiah, and S. I. Ito, “Mycogenic Selenium Nanoparticles as Potential New Generation Broad Spectrum Antifungal Molecules,” Biomolecules, vol. 9, no. 9, Sep. 2019, doi: 10.3390/BIOM9090419. [8] F. Mavandadnejad, E. Fa8079ghfuri, N. Mokhtari-Nori, S. Rezaie, and A. Shahverdi, “Antifungal activity of selenium nanoparticles and selenium disulfide against two Malassezia species,” American Research Journal of Dermatology, vol. 1, no. 1, 2019, doi: 10.21694/2642-2980.19002. [9] G. Godse and K. Godse, “Safety, Efficacy and Attributes of 2.5% Selenium Sulfide Shampoo in the Treatment of Dandruff: A Single-Center Study,” Cureus, vol. 16, no. 3, Mar. 2024, doi: 10.7759/CUREUS.57148. [10] S. S. Barve, S. Deshpande, and P. P. Dhawal, “Cytotoxic, cytostatic, and keratolytic activity of anti-dandruff shampoo formulations,” International Journal of Research in Dermatology Barve SS et al. Int J Res Dermatol, vol. 9, no. 2, pp. 61–66, 2023, doi: 10.18203/issn.2455-4529.IntJResDermatol20230036. [11] S. M. Joshi, S. De Britto, S. Jogaiah, and S. I. Ito, “Mycogenic Selenium Nanoparticles as Potential New Generation Broad Spectrum Antifungal Molecules,” Biomolecules, vol. 9, no. 9, Sep. 2019, doi: 10.3390/BIOM9090419.