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

Abstract

AIMTo investigate the efficacy of a chitosan/polyethylene glycol blended paste as a local antibiotic delivery device, particularly in musculoskeletal wounds.METHODSAcidic (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.RESULTSThe 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.CONCLUSIONCPP is an injectable, bioadhesive, biodegradable, and biocompatible material with potential to allow variable antibiotic loading and active, local antibiotic release to prevent bacterial contamination.