Liposomes-in-chitosan hydrogel boosts potential of chlorhexidine in biofilm eradication in vitro

Carbohydr Polym. 2021 Jun 15:262:117939. doi: 10.1016/j.carbpol.2021.117939. Epub 2021 Mar 16.

Abstract

Successful treatment of skin infections requires eradication of biofilms found in up to 90 % of all chronic wounds, causing delayed healing and increased morbidity. We hypothesized that chitosan hydrogel boosts the activity of liposomally-associated membrane active antimicrobials (MAA) and could potentially improve bacterial and biofilm eradication. Therefore, liposomes (∼300 nm) bearing chlorhexidine (CHX; ∼50 μg/mg lipid) as a model MAA were incorporated into chitosan hydrogel. The novel CHX-liposomes-in-hydrogel formulation was optimized for skin therapy. It significantly inhibited the production of nitric oxide (NO) in lipopolysaccharide (LPS)-induced macrophage and almost completely reduced biofilm formation. Moreover, it reduced Staphylococcus aureus and Pseudomonas aeruginosa adherent bacterial cells in biofilm by 64.2-98.1 %. Chitosan hydrogel boosted the anti-inflammatory and antimicrobial properties of CHX.

Keywords: Bacterial eradication; Chitosan; Lipid-based vesicle; Membrane active antimicrobials; Skin therapy.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology
  • Bacteria / drug effects
  • Biofilms / drug effects*
  • Chitosan / chemistry
  • Chitosan / pharmacology*
  • Chlorhexidine / chemistry
  • Chlorhexidine / pharmacology*
  • Humans
  • Hydrogels / chemistry
  • Hydrogels / pharmacology*
  • Lipopolysaccharides / metabolism
  • Liposomes / chemistry
  • Liposomes / pharmacology*
  • Macrophages / drug effects
  • Mice
  • Nitric Oxide / metabolism
  • Pseudomonas aeruginosa / drug effects
  • Skin Diseases, Bacterial / drug therapy
  • Staphylococcus aureus / drug effects
  • Wounds and Injuries / drug therapy

Substances

  • Anti-Bacterial Agents
  • Anti-Inflammatory Agents
  • Hydrogels
  • Lipopolysaccharides
  • Liposomes
  • Nitric Oxide
  • Chitosan
  • Chlorhexidine