Antimicrobial peptides-loaded smart chitosan hydrogel: Release behavior and antibacterial potential against antibiotic resistant clinical isolates

Int J Biol Macromol. 2020 Dec 1:164:855-862. doi: 10.1016/j.ijbiomac.2020.07.011. Epub 2020 Jul 6.

Abstract

In this study, we synthesized thermo-responsive chitosan (TCTS) hydrogels, and loaded with different concentrations of antimicrobial peptide (AMP) (0, 4, 8 and 16 μg·ml-1) to fabricate an antibacterial wound dressing against resistant clinical isolates. Physico-chemical properties, release behavior, cytobiocompatibility and antibacterial activity of the AMP-TCTS hydrogels against standard strain and resistant Acinetobacter baumannii were fully determined in vitro. The TCTS-40% β-glycerolphosphate hydrogels showed a gelation time of 15 min at 37 °C. 80% weight loss at day 35 with no changes in pH value was observed. AMP-TCTS hydrogels showed a burst release of AMP (around 40%) at day 1, and a controlled release up to day 7. A dramatic water uptake was observed at first 4 h, and then continued for 10 h in a steady manner. All the AMP-TCTS hydrogels showed excellent cytobiocompatibility for human fibroblasts. The TCTS showed no antibacterial activity against both standard strain and clinical isolates. All the AMP-TCTS hydrogels had strong antibacterial activity against standard strains, but only 16 μg·ml-1 showed antibacterial behavior against resistant A. baumannii. Our results strongly suggest the 16 μg·ml-1 AMP-TCTS hydrogel as an excellent antibacterial wound dressing against resistant A. baumannii, and now promises to proceed with pre-clinical investigations.

Keywords: Chitosan; Hydrogel; Resistant bacteria, post-wound infection; Thermos-responsive; Wound dressing.

MeSH terms

  • Acinetobacter baumannii
  • Anti-Bacterial Agents / pharmacology*
  • Bandages*
  • Biocompatible Materials
  • Cell Survival
  • Cells, Cultured
  • Chitosan / chemistry*
  • Drug Delivery Systems
  • Drug Resistance, Bacterial*
  • Fibroblasts
  • Humans
  • Hydrogels / chemistry*
  • Hydrogen-Ion Concentration
  • Microbial Sensitivity Tests
  • Pore Forming Cytotoxic Proteins / pharmacology*
  • Temperature
  • Water / chemistry

Substances

  • Anti-Bacterial Agents
  • Biocompatible Materials
  • Hydrogels
  • Pore Forming Cytotoxic Proteins
  • Water
  • Chitosan