Antimicrobial and Anti-Biofilm Activities of Surface Engineered Polycationic Albumin Nanoparticles with Reduced Hemolytic Activity

Macromol Biosci. 2018 Oct;18(10):e1800196. doi: 10.1002/mabi.201800196. Epub 2018 Aug 1.

Abstract

Protein-based polymeric polyelectrolytes are emerging as alternative synthetic nanoparticles owing to their biodegradability and biocompatibility. However, potential in vivo toxicity remains a significant challenge. Herein an array of protein polyelectrolytes generated from cationic human serum albumin (cHSA) and polyethylene glycol (PEG) are synthesized via synthetic customization as antimicrobials for the treatment of systemic infections. By varying PEG molecular weight and chain length, in vitro hemolytic activity can be fine-tuned without significantly affecting antimicrobial potency. The optimal hybrid material, PEG (2000)18 -cHSA, with potent antimicrobial character, low hemolytic activity, and in vitro biofilm disruptive properties is identified. Surface plasmon resonance (SPR) evaluation demonstrates significantly higher binding activity of the protein nanoparticles to bacteria cell wall components and microfluidic live-cell imaging indicates that the nanoparticles act through a membranolytic mechanism. Given their low susceptibility to drug resistance and potent activity against resistant bacteria strains, these findings establish the PEGylated albumin nanoparticles as a potent weaponry against drug resistance and biofilm-related infection.

Keywords: PEGylation; albumin; antimicrobial; biofilm; drug resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents* / chemical synthesis
  • Anti-Bacterial Agents* / chemistry
  • Anti-Bacterial Agents* / pharmacology
  • Bacteria / growth & development*
  • Bacterial Physiological Phenomena / drug effects*
  • Biofilms / drug effects*
  • Biofilms / growth & development
  • Candida albicans / physiology*
  • Erythrocytes / cytology
  • Erythrocytes / metabolism*
  • Hemolysis / drug effects*
  • Humans
  • Nanoparticles / chemistry*
  • Polyethylene Glycols / chemistry
  • Serum Albumin, Human* / chemistry
  • Serum Albumin, Human* / pharmacology

Substances

  • Anti-Bacterial Agents
  • Polyethylene Glycols
  • polyethylene glycol 2000
  • Serum Albumin, Human