Nitric oxide integrated polyethylenimine-based tri-block copolymer for efficient antibacterial activity

Biomaterials. 2013 Nov;34(34):8766-75. doi: 10.1016/j.biomaterials.2013.07.064. Epub 2013 Aug 6.

Abstract

The work demonstrated a successful synthesis of nitric oxide (NO)-releasing material and its antibacterial effect on Gram-negative Escherichia coli (E. coli), Gram-positive Staphylococcus aureus (S. aureus) and methicillin-resistant S. aureus (MRSA). The polymeric support composed of thermosensitive Pluronic F68 having good biocompatibility and branched polyethylenimine (BPEI) housed N-diazeniumdiolates (NONOates) which could store and release NO under appropriate physiological condition. The developed F68-BPEI-NONOates releases a sufficient amount of NO under physiological condition to elicit effective killing of E. coli, S. aureus and MRSA. The antibacterial ability of the released NO was compared to untreated control or unmodified F68 polymer by using confocal microscopy; F68-BPEI-NONOates demonstrated excellent antibacterial activity with in vitro low cytotoxicity. TEM investigation also revealed the destruction of bacteria membrane caused by NO. The effectiveness of F68-BPEI-NONOates against resistant strains such as MRSA provides a very simple but highly efficient strategy to combat drug-resistant bacterial infections.

Keywords: Antibacterial activity; Methicillin-resistance; N-Diazeniumdiolates; Nitric oxide delivery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Delayed-Action Preparations / pharmacology
  • Drug Delivery Systems
  • Drug Synergism
  • Escherichia coli / drug effects
  • Escherichia coli / growth & development
  • Methicillin-Resistant Staphylococcus aureus / drug effects
  • Methicillin-Resistant Staphylococcus aureus / growth & development
  • Mice
  • Microscopy, Confocal
  • Microscopy, Electron, Transmission
  • Nitric Oxide / pharmacology*
  • Polyethyleneimine / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Delayed-Action Preparations
  • Nitric Oxide
  • Polyethyleneimine