title: Evaluation of a chitosan-polyethylene glycol paste as a local antibiotic delivery device.
abstract: OBJECTIVE
  To investigate the efficacy of a chitosan/polyethylene glycol blended paste as a local antibiotic delivery device, particularly in musculoskeletal wounds.
  
  
  METHODS
  Acidic (A) chitosan sponges and neutralized (N) chitosan/polyethylene glycol (PEG) blended sponges were combined in ratios of 3A:2N, 1A:1N, and 2A:3N; then hydrated with phosphate buffered saline to form a chitosan/PEG paste (CPP). Bothin vitroandin vivostudies were conducted to determine the potential CPP has as a local antibiotic delivery device.In vitrobiocompatibility was assessed by the cytotoxic response of fibroblast cells exposed to the experimental groups. Degradation rate was measured as the change in dry mass due to lysozyme based degradation over a 10-d period. The antibiotic elution profiles and eluate activity of CPP were evaluated over a 72-h period. To assess thein vivoantimicrobial efficacy of the CPP, antibiotic-loaded paste samples were exposed to subcutaneously implanted murine catheters inoculated withStaphylococcus aureus. Material properties of the experimental paste groups were evaluated by testing the ejection force from a syringe, as well as the adhesion to representative musculoskeletal tissue samples.
  
  
  RESULTS
  The highly acidic CPP group, 3A:2N, displayed significantly lower cell viability than the control sponge group. The equally distributed group, 1A:1N, and the highly neutral group, 2A:3N, displayed similar cell viability to the control sponge group and are deemed biocompatible. The degradation studies revealed CPP is more readily degradable than the chitosan sponge control group. The antibiotic activity studies indicated the CPP groups released antibiotics at a constant rate and remained above the minimum inhibitory concentrations of the respective test bacteria for a longer time period than the control chitosan sponges, as well as displaying a minimized burst release. Thein vivofunctional model resulted in complete bacterial infection prevention in all catheters treated with the antibiotic loaded CPP samples. All experimental paste groups exhibited injectability and adhesive qualities that could be advantageous material properties for drug delivery to musculoskeletal injuries.
  
  
  CONCLUSIONS
  CPP is an injectable, bioadhesive, biodegradable, and biocompatible material with potential to allow variable antibiotic loading and active, local antibiotic release to prevent bacterial contamination.
authors.affiliation: Cheyenne S Rhodes, Christopher M Alexander, Joel M Berretta, Joel D Bumgardner, Warren O Haggard, J Amber Jennings, Department of Biomedical Engineering, University of Memphis, Memphis, TN 38152, United States.
authors.forename: Cheyenne S
authors.initials: CS
authors.lastname: Rhodes
authors.affiliation: Cheyenne S Rhodes, Christopher M Alexander, Joel M Berretta, Joel D Bumgardner, Warren O Haggard, J Amber Jennings, Department of Biomedical Engineering, University of Memphis, Memphis, TN 38152, United States.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Alexander
authors.affiliation: Cheyenne S Rhodes, Christopher M Alexander, Joel M Berretta, Joel D Bumgardner, Warren O Haggard, J Amber Jennings, Department of Biomedical Engineering, University of Memphis, Memphis, TN 38152, United States.
authors.forename: Joel M
authors.initials: JM
authors.lastname: Berretta
authors.affiliation: Cheyenne S Rhodes, Christopher M Alexander, Joel M Berretta, Joel D Bumgardner, Warren O Haggard, J Amber Jennings, Department of Biomedical Engineering, University of Memphis, Memphis, TN 38152, United States.
authors.forename: Harry S
authors.initials: HS
authors.lastname: Courtney
authors.affiliation: Cheyenne S Rhodes, Christopher M Alexander, Joel M Berretta, Joel D Bumgardner, Warren O Haggard, J Amber Jennings, Department of Biomedical Engineering, University of Memphis, Memphis, TN 38152, United States.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Beenken
authors.affiliation: Cheyenne S Rhodes, Christopher M Alexander, Joel M Berretta, Joel D Bumgardner, Warren O Haggard, J Amber Jennings, Department of Biomedical Engineering, University of Memphis, Memphis, TN 38152, United States.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Smeltzer
authors.affiliation: Cheyenne S Rhodes, Christopher M Alexander, Joel M Berretta, Joel D Bumgardner, Warren O Haggard, J Amber Jennings, Department of Biomedical Engineering, University of Memphis, Memphis, TN 38152, United States.
authors.forename: Joel D
authors.initials: JD
authors.lastname: Bumgardner
authors.affiliation: Cheyenne S Rhodes, Christopher M Alexander, Joel M Berretta, Joel D Bumgardner, Warren O Haggard, J Amber Jennings, Department of Biomedical Engineering, University of Memphis, Memphis, TN 38152, United States.
authors.forename: Warren O
authors.initials: WO
authors.lastname: Haggard
authors.affiliation: Cheyenne S Rhodes, Christopher M Alexander, Joel M Berretta, Joel D Bumgardner, Warren O Haggard, J Amber Jennings, Department of Biomedical Engineering, University of Memphis, Memphis, TN 38152, United States.
authors.forename: J Amber
authors.initials: JA
authors.lastname: Jennings
keywords: Bacterial infection; Biofilm; Chitosan; Local antibiotic delivery; Paste; Polyethylene glycol