Rapid microwave-based method for the preparation of antimicrobial lignin-capped silver nanoparticles active against multidrug-resistant bacteria

Int J Pharm. 2021 Mar 1:596:120299. doi: 10.1016/j.ijpharm.2021.120299. Epub 2021 Jan 30.

Abstract

Due to the increasing inability of antibiotics to treat multidrug-resistant (MDR) bacteria, metal and metal oxide nanoparticles have been gaining interest as antimicrobial agents. Among those, silver nanoparticles have been used extensively as broad-spectrum antimicrobial agents. Here, we describe a newly-developed, 10-min (120 °C at 5 bar pressure) microwave-assisted synthesis of silver nanoparticles made from the wood biopolymer lignin as a reducing and capping agent. The resulting lignin-capped silver nanoparticles (AgLNPs) had an average particle diameter of 13.4 ± 2.8 nm. Antimicrobial susceptibility assays against a variety of MDR clinical Gram-positive and Gram-negative pathogens revealed a minimal inhibitory concentration (MIC) of AgLNPs ≤5 µg/mL. AgLNPs (10 µg/mL) showed ≤20% cytotoxicity towards monocytic THP-1 cells and were well tolerated when administered subcutaneously in mice at high concentrations (5 mg at a concentration of 100 mg/mL) with no obvious toxicity. AgLNPs showed efficacy in an in vivo infection (abscess) mouse model against MDR Pseudomonas aeruginosa LESB58 and methicillin-resistant Staphylococcus aureus USA300. A significant decrease in abscess sizes was observed for both strains as well as a reduction in bacterial loads of P. aeruginosa after three days. This demonstrates that microwave-assisted synthesis provides an optimized strategy for the production of AgLNPs while maintaining antimicrobial activity in vitro and in vivo.

Keywords: Broad-spectrum activity; Microwave; Pseudomonas; Silver nanoparticles; Skin infection; Staphylococcus; Wood biopolymer.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Anti-Infective Agents*
  • Lignin
  • Metal Nanoparticles*
  • Methicillin-Resistant Staphylococcus aureus*
  • Mice
  • Microbial Sensitivity Tests
  • Microwaves
  • Pseudomonas aeruginosa
  • Silver

Substances

  • Anti-Bacterial Agents
  • Anti-Infective Agents
  • Silver
  • Lignin