Blended Chitosan Paste for Infection Prevention: Preliminary and Preclinical Evaluations

Abstract

The preliminary studies with the chitosan paste delivered antibiotics to a contaminated musculoskeletal wound with hardware and prevented infection. More studies in a complex musculoskeletal wound and dosage studies are needed for continued development.

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].…”

“…The first derivative was N-trimethyl chitosan (TMC), a quaternized chitosan derivative, and the other derivative was poly(ethylene glycol) diacrylate chitosan (PEGDAc), a graft copolymer of chitosan. 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].…”

“…Two controls were prepared for comparison to the developed system: an injectable paste and lyophilized sponges. Berretta et al previously developed an injectable system and was prepared according to their methods [25]. Blended chitosan control paste was prepared by dissolving 1% chitosan (w./v.)…”

“…A primary goal of this research was to reduce the mismatch between elution kinetics and degradation rates that affects chitosan-based delivery systems [7]. Elution kinetics for these systems typically exhibit an initial bolus release that is followed by low levels of release until the system is degraded [25,39]. PEGDA has previously been investigated as a crosslinked hydrogel and a cross-linking agent with a variety of systems to sustain drug delivery [21,40,41].…”

“…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].…”