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Pluronic F-127 Enhances the Antifungal Activity of Fluconazole against Resistant Candida Strains

Katarzyna Malec1, Aleksandra Mikołajczyk2, Dominik Marciniak1

  • 1Department of Drug Form Technology, Faculty of Pharmacy, Wroclaw Medical University, 211a Borowska Str, 50-556 Wroclaw, Poland.

ACS Infectious Diseases
|December 18, 2023
PubMed

Insights

Pluronic F-127 (PLX) enhanced fluconazole (FLU) efficacy against resistant Candida strains. Higher PLX concentrations improved antifungal activity, suggesting potential for topical FLU formulations.

Area of Science:

  • Mycology and Pharmaceutical Sciences
  • Antimicrobial Resistance Research

Background:

  • Drug-resistant Candida strains are a major clinical challenge, necessitating novel therapeutic strategies.
  • Limited topical fluconazole (FLU) formulations exist, despite its common use.
  • Polymeric excipients may modulate multidrug resistance mechanisms in fungi.

Purpose of the Study:

  • To evaluate Pluronic F-127 (PLX) formulations for enhancing susceptibility of resistant Candida to FLU.
  • To determine the correlation between PLX concentration and antifungal efficacy.
  • To investigate the mode of action of PLX in potentiating FLU's antifungal activity.

Main Methods:

  • Development and testing of Pluronic F-127 (PLX) based formulations containing fluconazole (FLU).
  • Assessment of yeast growth inhibition in resistant Candida strains incubated with PLX/FLU formulations.
  • Gene expression analysis (CDR1/CDR2) to elucidate the mechanism of resistance modulation.

Main Results:

  • PLX-loaded FLU formulations demonstrated statistically significant inhibition of yeast growth.
  • Optimal antifungal efficacy was observed with 5.0% and 10.0% w/v PLX concentrations.
  • Upregulation of CDR1/CDR2 genes in Candida strains confirmed drug efflux as a primary resistance mechanism.

Conclusions:

  • Pluronic F-127 shows promise in overcoming fluconazole resistance in Candida.
  • PLX concentration directly influences the antifungal efficacy of fluconazole formulations.
  • PLX may interfere with the efflux pump mechanism contributing to Candida drug resistance.
Keywords:
Candida spp.PluronicPoloxamerefflux pumpfluconazoleresistant yeasts

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