Formulation and candidacidal activity of magnetic nanoparticles coated with cathelicidin LL-37 and ceragenin CSA-13

Sci Rep. 2017 Jul 4;7(1):4610. doi: 10.1038/s41598-017-04653-1.

Abstract

Fungal infections caused by Candida spp. represent an emerging problem during treatment of immunocompromised patients and those hospitalized with serious principal diseases. The ever-growing number of fungal strains exhibiting drug resistance necessitates the development of novel antimicrobial therapies including those based on membrane-permeabilizing agents and nanomaterials as drug carriers. In this study, the fungicidal activities of LL-37 peptide, ceragenin CSA-13 and its magnetic derivatives (MNP@LL-37, MNP@CSA-13) against laboratory and clinical strains of C. albicans, C. glabrata and C. tropicalis were evaluated. These experiments confirm the high anti-fungal activity of these well-characterized agents mediated by their interaction with the fungal membrane and demonstrate elevated activity following immobilization of LL-37 and CSA-13 on the surface of magnetic nanoparticles (MNPs). Furthermore, MNP-based nanosystems are resistant to inhibitory factors present in body fluids and effectively inhibit formation of fungal biofilm. Simultaneously, synthesized nanostructures maintain immunomodulatory properties, described previously for free LL-37 peptide and CSA-13 substrate and they do not interfere with the proliferation and viability of osteoblasts, confirming their high biocompatibility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents / chemical synthesis
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology*
  • Antimicrobial Cationic Peptides / chemistry
  • Antimicrobial Cationic Peptides / pharmacology*
  • Biofilms / drug effects
  • Candida / drug effects*
  • Candida / isolation & purification
  • Candidiasis / drug therapy
  • Candidiasis / microbiology
  • Cathelicidins
  • Cell Line
  • Cell Membrane / drug effects
  • Cell Proliferation
  • Drug Compounding
  • Humans
  • Magnetite Nanoparticles / chemistry*
  • Microbial Sensitivity Tests
  • Osteoblasts / cytology
  • Osteoblasts / drug effects
  • Steroids / chemistry
  • Steroids / pharmacology*

Substances

  • Antifungal Agents
  • Antimicrobial Cationic Peptides
  • Magnetite Nanoparticles
  • Steroids
  • ceragenin CSA-13
  • Cathelicidins