Evaluation of a chitosan-polyethylene glycol paste as a local antibiotic delivery device

作     者：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 

作者机构：Department of Biomedical EngineeringUniversity of Memphis Department of MedicineUniversity of Tennessee Health Science CenterVeterans Affairs Medical Center Department of Microbiology and ImmunologyUniversity of Arkansas for Medical Sciences 

出 版 物：《世界骨科杂志：英文版》 

年 卷 期：2017年第8卷第2期

页      面：130-141页

学科分类：0403[教育学-体育学] 1007[医学-药学(可授医学、理学学位)] 100705[医学-微生物与生化药学] 1002[医学-临床医学] 10[医学] 

基　　金：Supported by National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health No.R01AR066050 

主　　题：Chitosan Polyethylene glycol Paste Local antibiotic delivery Biofilm Bacterial infection 

摘      要：AIM To investigate the efficacy of a chitosan/polyethylene glycol blended paste as a local antibiotic delivery device, particularly in musculoskeletal *** 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 *** 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 tr