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Enhanced clearing of Candida biofilms on a 3D urothelial cell in vitro model using lysozyme-functionalized

Anheng Wang1, Paul J Weldrick1, Leigh A Madden2

  • 1Department of Chemistry, University of Hull, Cottingham Road, Hull, HU67RX, UK.

Biomaterials Science
|September 16, 2021
PubMed

Insights

Researchers developed a novel 3D cell model to test nanoparticle antifungal treatments against Candida urinary tract biofilms. This model shows promise for evaluating nanotherapeutics and potentially replacing animal studies.

Area of Science:

  • Biomedical Engineering
  • Mycology
  • Nanotechnology

Background:

  • Nosocomial urinary tract infections caused by Candida biofilms are increasing, particularly in immunocompromised patients.
  • Indwelling devices serve as a significant source for these infections, bridging external contaminants with the internal environment.
  • Nanoparticle (NP)-based therapeutics show potential against antibiotic-resistant biofilms, but clinical translation is hindered by a lack of precise testing models.

Purpose of the Study:

  • To develop a novel 3D human urothelial cell culture model for studying Candida urinary tract biofilm infections.
  • To evaluate the efficacy of a novel nanoparticle (NP)-based antifungal therapeutic formulation in this model.
  • To provide a reliable in vitro platform for testing nanotherapeutic delivery against fungal biofilms.

Main Methods:

  • Development of a 3D human urothelial cell culture model mimicking biofilm infections.
  • Formulation of nanoparticle (NP) therapeutics: shellac cores loaded with fluconazole and coated with lysozyme.
  • Testing the efficiency and toxicity of the NP formulation on Candida albicans biofilms in the 3D model.

Main Results:

  • The developed 3D urothelial cell model successfully supported Candida biofilm formation.
  • The novel NP formulation (0.2 wt% lysozyme-coated 0.02 wt% fluconazole-loaded 0.2 wt% shellac NPs, stabilized by 0.25 wt% poloxamer 407) demonstrated enhanced efficacy in removing Candida albicans biofilms.
  • The NP formulation exhibited low toxicity to the urothelial cells.

Conclusions:

  • A reproducible and reliable 3D in vitro model for Candida urinary tract biofilm infections has been established.
  • The novel NP formulation is effective against Candida biofilms with minimal urothelial cell toxicity.
  • This model could accelerate the clinical application of antifungal nanotherapeutics by providing a viable alternative to animal testing.

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