Novel hybrid system based on carboxymethyl chitosan hydrogel encapsulating drug loaded nanoparticles for prolonged release of Vancomycin in the treatment of bacterial infection.

Abstract

Current bacterial infections clinical treatments, such as intravenous antibiotic administration and local injection, suffer from short action duration, repeated administrations, and severe cell toxicity. To address these limitations, it is imperative to develop sustained drug release system with prolonged antimicrobial effects. In this work, a hybrid system was prepared using EDC/NHS catalyzed crosslinking-based carboxymethyl chitosan (CMCS) hydrogel as a carrier to encapsulate biodegradable nanoparticles (NPs) loaded with vancomycin, an efficient antibacterial drug. First, ring opening polymerization of L-lactide or L-lactide/glycolide mixture was performed in the presence of poly(ethylene glycol) (PEG) to yield PEG-PLA or PEG-PLGA block copolymers. Vancomycin was loaded in PEG-PLA or PEG-PLGA NPs using double emulsion method. Drug-loaded NPs were then encapsulated in the CMCS hydrogel. Drug release from NPs, CMCS hydrogel and hybrid NPs-hydrogel systems was performed, and release kinetics were analyzed using Korsmeyer-Peppas model. The established hybrid system exhibited prolonged drug release without burst release. Finally, the biocompatibility of the hybrid system was evidenced by the MTT, hemolysis, dynamic clotting time, and zebrafish embryotoxicity tests. Last but not least, the hybrid system displayed outstanding long-lasting antimicrobial activity as shown by co-culture with Monoclonal S. aureus, thus suggesting great potential for applications in bacterial infection treatment.