Antimicrobial peptide Temporin-L complexed with anionic cyclodextrins results in a potent and safe agent against sessile bacteria

Int J Pharm. 2020 Jun 30:584:119437. doi: 10.1016/j.ijpharm.2020.119437. Epub 2020 May 21.

Abstract

Concern over antibiotic resistance is growing, and new classes of antibiotics, particularly against Gram-negative bacteria, are needed. Antimicrobial peptides (AMPs) have been proposed as a new class of clinically useful antimicrobials. Special attention has been devoted to frog-skin temporins. In particular, temporin L (TL) is strongly active against Gram-positive, Gram-negative bacteria and yeast strains. With the aim of overcoming some of the main drawbacks preventing the widespread clinical use of this peptide, i.e. toxicity and unfavorable pharmacokinetics profile, we designed new formulations combining TL with different types of cyclodextrins (CDs). TL was associated to a panel of neutral or negatively charged, monomeric and polymeric CDs. The impact of CDs association on TL solubility, as well as the transport through bacterial alginates was assessed. The biocompatibility on human cells together with the antimicrobial and antibiofilm properties of TL/CD systems was explored.

Keywords: Antibiofilm agents; Antibiotic resistance; Antimicrobial peptides; Cyclodextrins.

MeSH terms

  • Alginates / chemistry
  • Anti-Infective Agents / administration & dosage
  • Anti-Infective Agents / chemistry*
  • Antimicrobial Cationic Peptides / administration & dosage
  • Antimicrobial Cationic Peptides / chemistry*
  • Bacteria / drug effects
  • Bacteria / growth & development
  • Bacterial Physiological Phenomena / drug effects
  • Biofilms / drug effects
  • Cell Line
  • Cell Survival / drug effects
  • Cyclodextrins / administration & dosage
  • Cyclodextrins / chemistry*
  • Humans
  • Models, Molecular
  • Solubility

Substances

  • Alginates
  • Anti-Infective Agents
  • Antimicrobial Cationic Peptides
  • Cyclodextrins
  • temporin