Targeting and synergistic action of an antifungal peptide in an antibiotic drug-delivery system

J Control Release. 2017 Jun 28:256:46-55. doi: 10.1016/j.jconrel.2017.04.023. Epub 2017 Apr 18.

Abstract

Amphotericin B (AmB) has been widely used against fungal infections throughout almost the entire body, including the skin, nails, oral cavity, respiratory tract, and urinary tract. However, the development of AmB-loaded nanoparticles demands a novel technique that reduces its toxicity and other associated problems. Here, we developed a pH-responsive and redox-sensitive polymer-based AmB-delivery carrier system. In particular, this system was functionalized by conjugation with the antifungal peptide histatin 5, which acts both as a targeting ligand and a synergistic antifungal molecule against Candida albicans, a major systemic fungal pathogen of humans. Our results in vitro and in vivo suggest that this drug-delivery system may serve as a novel tool to facilitate the use of antimicrobial peptides as targeting ligands to pathogenic microbes, which would open new avenues of investigation in the field of drug delivery.

Keywords: Amphotericin B; Antifungal peptide; Candida albicans; Histatin 5; Targeted drug delivery system.

MeSH terms

  • Amphotericin B / administration & dosage*
  • Amphotericin B / chemistry
  • Amphotericin B / pharmacology
  • Amphotericin B / therapeutic use
  • Animals
  • Anti-Bacterial Agents
  • Antifungal Agents / administration & dosage*
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology
  • Antifungal Agents / therapeutic use
  • Candida albicans / drug effects
  • Candida albicans / growth & development
  • Candidiasis / drug therapy
  • Cell Line
  • Cell Survival / drug effects
  • Cysteamine / chemistry
  • Drug Delivery Systems*
  • Drug Liberation
  • Drug Synergism
  • Erythrocytes / drug effects
  • Female
  • Hemolysis / drug effects
  • Histatins / administration & dosage*
  • Histatins / chemistry
  • Histatins / pharmacology
  • Histatins / therapeutic use
  • Humans
  • Mice, Inbred ICR
  • Polymers / chemistry
  • Rats

Substances

  • Anti-Bacterial Agents
  • Antifungal Agents
  • HTN3 protein, human
  • Histatins
  • Polymers
  • Cysteamine
  • Amphotericin B