Pluronic® F-127 enhances antifungal activity of fluconazole against resistant Candida strains

Malec, Katarzyna, Mikołajczyk, Aleksandra, Marciniak, Dominik, Gawin-Mikołajewicz, Agnieszka, Matera-Witkiewicz, Agnieszka, Karolewicz, Bożena, Nawrot, Urszula, Khimyak, Yaroslav Z. ORCID: https://orcid.org/0000-0003-0424-4128 and Nartowski, Karol P. (2024) Pluronic® F-127 enhances antifungal activity of fluconazole against resistant Candida strains. ACS Infectious Diseases, 10 (1). pp. 215-231. ISSN 2373-8227

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Abstract

Candida strains as the most frequent causes of infections, along with their increased drug resistance, pose significant clinical and financial challenges to the healthcare system. Some polymeric excipients were reported to interfere with the multidrug resistance mechanism. Bearing in mind that there are a limited number of marketed products with fluconazole (FLU) for the topical route of administration, Pluronic F-127 (PLX)/FLU formulations were investigated in this work. The aims of this study were to investigate (i) whether PLX-based formulations can increase the susceptibility of resistant Candida strains to FLU, (ii) whether there is a correlation between block polymer concentration and the antifungal efficacy of the FLU-loaded PLX formulations, and (iii) what the potential mode of action of PLX assisting FLU is. The yeast growth inhibition upon incubation with PLX formulations loaded with FLU was statistically significant. The highest efficacy of the azole agent was observed in the presence of 5.0 and 10.0% w/v of PLX. The upregulation of the CDR1/CDR2 genes was detected in the investigated Candida strains, indicating that the efflux of the drug from the fungal cell was the main mechanism of the resistance.

Item Type: Article
Additional Information: Funding Information: K.M. would like to acknowledge funding from the National Science Centre in Poland (ETIUDA: 2019/32/T/NZ7/00246). The funding for the materials was obtained by the Ministry of Education and Science in Poland (internal number at WMU: SUB.D250.22.018).
Uncontrolled Keywords: resistant yeasts,candida spp.,efflux pump,poloxamer,pluronic,fluconazole,infectious diseases ,/dk/atira/pure/subjectarea/asjc/2700/2725
Faculty \ School: Faculty of Science > School of Pharmacy
UEA Research Groups: Faculty of Science > Research Groups > Pharmaceutical Materials and Soft Matter
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Depositing User: LivePure Connector
Date Deposited: 04 Mar 2024 18:33
Last Modified: 04 Mar 2024 18:34
URI: https://ueaeprints.uea.ac.uk/id/eprint/94504
DOI: 10.1021/acsinfecdis.3c00536

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