Cell penetrating peptides as efficient nanocarriers for delivery of antifungal compound, natamycin for the treatment of fungal keratitis

Pharm Res. 2015 Jun;32(6):1920-30. doi: 10.1007/s11095-014-1586-x. Epub 2014 Dec 3.

Abstract

Purpose: Enhancing the penetration ability of the antifungal drug natamycin, known to possess poor penetration ability through the corneal epithelium, by complexing with cell penetrating peptides.

Methods: The drug, natamycin was conjugated to a cell penetrating peptide, Tat-dimer (Tat2). The uptake ability of the conjugate in human corneal epithelial cells and its antifungal activity against filamentous fungi, F.solani has been elucidated.

Results: The cellular penetration ability of natamycin increased upon conjugation with Tat2. The conjugation between natamycin and Tat2 also lead to enhanced solubility of the drug in aqueous medium. The antifungal activity of the conjugate increased two- folds in comparison to unconjugated natamycin against clinical isolates of F.solani.

Conclusion: The formation of CPP-natamycin complex is clinically significant as it may enhance the bioavailability of natamycin in corneal tissues and aid in efficient management of fungal keratitis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Antifungal Agents / administration & dosage
  • Antifungal Agents / chemistry
  • Antifungal Agents / metabolism
  • Antifungal Agents / pharmacology*
  • Cell-Penetrating Peptides / chemistry
  • Cell-Penetrating Peptides / metabolism*
  • Chemistry, Pharmaceutical
  • Drug Carriers*
  • Epithelium, Corneal / drug effects
  • Epithelium, Corneal / metabolism
  • Epithelium, Corneal / microbiology
  • Eye Infections, Fungal / drug therapy*
  • Eye Infections, Fungal / metabolism
  • Eye Infections, Fungal / microbiology
  • Fungi / drug effects
  • HeLa Cells
  • Humans
  • Keratitis / drug therapy*
  • Keratitis / metabolism
  • Keratitis / microbiology
  • Nanotechnology
  • Natamycin / administration & dosage
  • Natamycin / chemistry
  • Natamycin / metabolism
  • Natamycin / pharmacology*
  • Particle Size
  • Solubility
  • Technology, Pharmaceutical / methods

Substances

  • Antifungal Agents
  • Cell-Penetrating Peptides
  • Drug Carriers
  • Natamycin