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

Katarzyna Malec, Aleksandra Mikołajczyk, Dominik Marciniak, Agnieszka Gawin-Mikołajewicz, Agnieszka Matera-Witkiewicz, Bożena Karolewicz, Urszula Nawrot, Yaroslav Z. Khimyak, Karol P. Nartowski

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)215-231
Number of pages17
JournalACS Infectious Diseases
Volume10
Issue number1
Early online date18 Dec 2023
DOIs
Publication statusPublished - 12 Jan 2024

Keywords

  • resistant yeasts
  • Candida spp.
  • efflux pump
  • Poloxamer
  • Pluronic
  • fluconazole

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