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.

Characterization of trimethyl chitosan/polyethylene glycol derivatized chitosan blend as an injectable and degradable antimicrobial delivery system

“…In preliminary work not contained in this manuscript, our group showed that PEGDAc had twice the swelling ratio of unmodified chitosan, and other groups have produced similar results [21,40]. This could help explain the extended release profile observed compared to unmodified chitosan and other injectable chitosan paste studies [25,26]. The extended release profile observed in Chen et al's study of a thiolated chitosan, PEGDA, and β-glycerophosphate complex is similar to the current study [21].…”

“…Unmodified chitosan delivery systems previously developed in this lab were prepared using the same batch of chitosan and used as controls [24,25]. Previous evaluations demonstrated that chitosan with this molecular weight and degree of deacetylation has favorable biocompatibility and degradation properties for local delivery of antimicrobials [25,26].…”

“…Previous studies demonstrated release of vancomycin and amikacin from unmodified chitosan pastes for 3 days, but the observed degradation rates did not correspond to their elution kinetics. Berretta et al showed almost complete degradation after day 2, and Rhodes et al showed degradation for 10 days without complete degradation [25,26]. Qu et al and Zhao et al developed chitosan-based hydrogels that were susceptible to hydrolytic degradation, and they showed approximately 50% degradation in PBS after 4 and 6 weeks, respectively [47,48].…”

“…Force values reported in this study are almost 10 times lower than this threshold value. Previous studies that have investigated injectable chitosan paste reported values for ejection force ranging from 30-150N [25,26]. Injectability of the system allows for complete coverage of open fractures that may possess complex geometries.…”

Development and Evaluation of an Injectable Chitosan/β-Glycerophosphate Paste as a Local Antibiotic Delivery System for Trauma Care

“…Lyophilized chitosan sponges were developed and are capable of local therapeutic antibiotic release, but they have limited ability to conform to complex wound morphologies, as well as an unwanted initial burst release of loaded antibiotics [17,18,19]. To address the limitations of chitosan sponges, an injectable paste of finely ground, lyophilized chitosan hydrated with antibiotic solution has been developed and has shown potential as an adjunctive infection-prevention tool [20,21]. The chitosan paste eluted inhibitory levels of antibiotics for 3 days, degraded in a similar time frame, and improved wound coverage.…”