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Antifungal activity of amphotericin B conjugated to carbon nanotubes

Monica Benincasa1, Sabrina Pacor, Wei Wu

  • 1Department of Life Sciences, University of Trieste, Italy.

ACS Nano
|December 15, 2010
PubMed

Insights

Functionalized carbon nanotubes (f-CNTs) conjugated with Amphotericin B (AMB) show potent antifungal activity, even against resistant strains. These f-CNT-AMB conjugates demonstrate reduced toxicity, offering a promising alternative for treating invasive fungal infections.

Area of Science:

  • * Nanotechnology and Materials Science
  • * Pharmaceutical Sciences
  • * Mycology

Background:

  • * Amphotericin B (AMB) is a primary antifungal agent but suffers from poor solubility and dose-dependent nephrotoxicity.
  • * Existing formulations like AMBD, liposomes, and lipid complexes aim to mitigate AMB's limitations.
  • * Functionalized carbon nanotubes (f-CNTs) offer novel drug delivery potential for enhanced therapeutic efficacy.

Purpose of the Study:

  • * To develop and evaluate novel Amphotericin B-functionalized carbon nanotube conjugates (f-CNT-AMB).
  • * To assess the in vitro antifungal activity and mechanism of action of f-CNT-AMB conjugates.
  • * To investigate the cytotoxicity of f-CNT-AMB conjugates on human cells.

Main Methods:

  • * Synthesis of two distinct f-CNT-AMB conjugates.
  • * Determination of minimum inhibitory concentration (MIC) against reference and clinical fungal strains.
  • * Evaluation of antifungal activity compared to AMB and AMBD.
  • * Investigation of the mechanism of action, focusing on membrane permeabilization.
  • * Cytotoxicity assessment on Jurkat cells.

Main Results:

  • * f-CNT-AMB conjugates exhibited antifungal activity comparable to or superior to AMB and AMBD.
  • * Candida strains resistant to AMBD were susceptible to f-CNT-AMB 1.
  • * The mechanism of action appears to be nonlytic, involving delayed membrane permeabilization.
  • * f-CNT-AMB 1 demonstrated no significant toxicity to Jurkat cells at effective antifungal concentrations.

Conclusions:

  • * f-CNT-AMB conjugates represent a promising strategy to enhance AMB's therapeutic profile.
  • * These novel conjugates offer potent antifungal activity and improved safety, addressing key limitations of conventional AMB formulations.
  • * Nanotechnology-based drug delivery systems hold significant potential for combating invasive fungal infections.

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