Hydrogels Containing Antibiofilm and Antimicrobial Agents Beneficial for Biofilm-Associated Wound Infection: Formulation Characterizations and In vitro Study

AAPS PharmSciTech. 2018 Apr;19(3):1219-1230. doi: 10.1208/s12249-017-0937-4. Epub 2017 Dec 26.

Abstract

Bacterial biofilm which adheres onto wound surface is shown to be impervious to antibiotics and this in turn delays wound healing. Previous studies showed that antibiofilm agents such as xylitol and ethylenediaminetetraacetic acid (EDTA) prevent bacterial adherence onto surfaces. Formulation of a wound dressing containing antibiofilm agents may be a plausible strategy in breaking the biofilm on wound surfaces and at the same time increase the efficacy of the antibiotic. The purpose of this study was to develop hydrogel formulations containing antibiofilm agents along with antibiotic (gentamicin) for bacterial biofilm-associated wound infection. Sodium carboxymethyl cellulose (NaCMC) hydrogels loaded with antibiofilm agents and antibiotic were prepared. The hydrogels were characterized for their physical properties, rheology, Fourier transform infrared spectroscopy (FTIR), drug content uniformity, differential scanning calorimetry (DSC) and in vitro drug release study. The antibiofilm (Crystal Violet staining and XTT assay) and antibacterial performances of the hydrogels against Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, and Escherichia coli were assessed in vitro. The formulated hydrogels showed adequate release of both antibiofilm agents (xylitol and EDTA). Both antimicrobial and antibiofilm tests showed promising results and demonstrated that the combination of xylitol, EDTA, and gentamicin had an additive effect against both Gram-positive and Gram-negative bacteria. In summary, NaCMC (sodium carboxymethyl cellulose) hydrogels containing the combination of antimicrobial and antibiofilm agents were successfully developed and this can be a new strategy in combating biofilm in wound infection which in turn accelerate wound healing.

Keywords: EDTA; antibiofilm agent; biofilm; hydrogel; xylitol.

MeSH terms

  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / therapeutic use
  • Bacterial Infections / drug therapy
  • Biofilms / drug effects*
  • Carboxymethylcellulose Sodium / chemistry
  • Drug Carriers / chemistry*
  • Drug Liberation
  • Edetic Acid / administration & dosage
  • Gram-Negative Bacteria / drug effects
  • Gram-Positive Bacteria / drug effects
  • Humans
  • Hydrogels / chemistry*
  • Wound Healing / drug effects
  • Wound Infection / drug therapy
  • Xylitol / administration & dosage

Substances

  • Anti-Bacterial Agents
  • Drug Carriers
  • Hydrogels
  • Edetic Acid
  • Carboxymethylcellulose Sodium
  • Xylitol