LL37 Microspheres Loaded on Activated Carbon-chitosan Hydrogel: Anti-bacterial and Anti-toxin Wound Dressing for Chronic Wound Infections

AAPS PharmSciTech. 2024 May 13;25(5):110. doi: 10.1208/s12249-024-02826-6.

Abstract

Antimicrobial peptide LL37 is a promising antibacterial candidate due to its potent antimicrobial activity with no known bacterial resistance. However, intrinsically LL37 is susceptible to degradation in wound fluids limits its effectiveness. Bacterial toxins which are released after cell lysis are found to hinder wound healing. To address these challenges, encapsulating LL37 in microspheres (MS) and loading the MS onto activated carbon (AC)-chitosan (CS) hydrogel. This advanced wound dressing not only protects LL37 from degradation but also targets bacterial toxins, aiding in the healing of chronic wound infections. First, LL37 MS and LL37-AC-CS hydrogel were prepared and characterised in terms of physicochemical properties, drug release, and peptide-polymer compatibility. Antibacterial and antibiofilm activity, bacterial toxin elimination, cell migration, and cell cytotoxicity activities were investigated. LL37-AC-CS hydrogel was effective against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. LL37-AC-CS hydrogel bound more endotoxin than AC with CS hydrogel alone. The hydrogel also induced cell migration after 72 h and showed no cytotoxicity towards NHDF after 72 h of treatment. In conclusion, the LL37-AC-CS hydrogel was shown to be a stable, non-toxic advanced wound dressing method with enhanced antimicrobial and antitoxin activity, and it can potentially be applied to chronic wound infections to accelerate wound healing.

Keywords: activated carbon; antimicrobial peptide LL37; bacterial toxins; infected wound; wound healing.

MeSH terms

  • Anti-Bacterial Agents* / administration & dosage
  • Anti-Bacterial Agents* / chemistry
  • Anti-Bacterial Agents* / pharmacology
  • Antimicrobial Cationic Peptides / administration & dosage
  • Antimicrobial Cationic Peptides / chemistry
  • Antimicrobial Cationic Peptides / pharmacology
  • Bacterial Toxins
  • Bandages*
  • Biofilms / drug effects
  • Carbon / chemistry
  • Cathelicidins
  • Cell Movement / drug effects
  • Chitosan* / chemistry
  • Drug Liberation
  • Escherichia coli* / drug effects
  • Humans
  • Hydrogels* / chemistry
  • Hydrogels* / pharmacology
  • Microbial Sensitivity Tests / methods
  • Microspheres*
  • Pseudomonas aeruginosa* / drug effects
  • Staphylococcus aureus* / drug effects
  • Wound Healing / drug effects
  • Wound Infection / drug therapy
  • Wound Infection / microbiology
  • Wound Infection / prevention & control

Substances

  • Chitosan
  • Anti-Bacterial Agents
  • Hydrogels
  • Antimicrobial Cationic Peptides
  • Cathelicidins
  • Bacterial Toxins
  • Carbon