Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Orthop. Feb 18, 2017; 8(2): 130-141
Published online Feb 18, 2017. doi: 10.5312/wjo.v8.i2.130
Evaluation of a chitosan-polyethylene glycol paste as a local antibiotic delivery device
Cheyenne S Rhodes, Christopher M Alexander, Joel M Berretta, Harry S Courtney, Karen E Beenken, Mark S Smeltzer, Joel D Bumgardner, Warren O Haggard, J Amber Jennings
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
Harry S Courtney, Department of Medicine, University of Tennessee Health Science Center, Veterans Affairs Medical Center, Memphis, TN 38103, United States
Karen E Beenken, Mark S Smeltzer, Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, AR 72204, United States
Author contributions: Rhodes CS and Berretta JM performed experiments and analyzed data; Alexander CM wrote the report; Beenken KE and Smeltzer MS planned and assisted with animal experiments; Courtney HS, Bumgardner JD, Haggard WO, and Jennings JA assisted with materials formulation, planning experiments, and data analysis; and all the authors contributed to this article.
Supported by National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health, No. R01AR066050 (The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health).
Institutional review board statement: The study was reviewed and approved by the University of Arkansas for Medical Sciences institutional review board.
Institutional animal care and use committee statement: Animal studies were approved by the institutional review board at the University of Arkansas for Medical Sciences (IACUC protocol #3540) and followed the IACUC guidelines.
Conflict-of-interest statement: No conflict exists among the authors of this manuscript and the findings of the report, to the best of our knowledge.
Data sharing statement: Technical appendix, statistical analysis, and dataset available from the corresponding author at chris.alexander@memphis.edu.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Christopher M Alexander, Graduate Research Assistant, Department of Biomedical Engineering, University of Memphis, 330 Technology Building, Memphis, TN 38152, United States. chris.alexander@memphis.edu
Telephone: +1-865-8099219
Received: June 17, 2016
Peer-review started: June 19, 2016
First decision: July 27, 2016
Revised: September 23, 2016
Accepted: November 16, 2016
Article in press: November 18, 2016
Published online: February 18, 2017
Abstract
AIM

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). Both in vitro and in vivo studies were conducted to determine the potential CPP has as a local antibiotic delivery device. In vitro biocompatibility 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 the in vivo antimicrobial efficacy of the CPP, antibiotic-loaded paste samples were exposed to subcutaneously implanted murine catheters inoculated with Staphylococcus 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. The in vivo functional 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.

CONCLUSION

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.

Keywords: Chitosan, Polyethylene glycol, Paste, Local antibiotic delivery, Biofilm, Bacterial infection

Core tip: The study investigates the efficacy of a chitosan-polyethylene glycol paste as a local antibiotic delivery device to prevent bacterial infection, particularly in high risk, severe musculoskeletal wounds complex in shape and experiencing decreased vascularity. Research focusing on three different paste formulations categorized by the ratio of acidic to neutral components involved in vitro evaluation of the paste cytotoxicity, degradation, antibiotic elution, as well as an in vivo functional infection model evaluating the antimicrobial efficacy of the paste. Preliminary study outcomes demonstrate the potential of a chitosan-polyethylene glycol paste as a local antibiotic delivery device capable of infection prevention.