Vancomycin-loaded oxidized hyaluronic acid and adipic acid dihydrazide hydrogel: Bio-compatibility, drug release, antimicrobial activity, and biofilm model

Abstract

Background: Prosthesis infection is a difficult-to-treat situation. Hydrogel is a novel biomaterial, which can be applied by simply spraying or by coating on implants before surgery and can be easily mixed with antibiotics. Methods: In order to evaluate the potential use of antibiotic-loaded hydrogel, we incorporated vancomycin into oxidized hyaluronic acid (HA) and adipic acid dihydrazide and evaluated the drug release and antimicrobial activity against methicillin-resistant Staphylococcus aureus (ATCC 29213). Results: The average release percentage of vancomycin on day 3 was about 86%. The antibiotic-loaded gel was biocompatible with mesenchymal stem cell, MC3T3, and L929 cell lines. The in vitro inhibition zones of vancomycin-loaded hydrogel [500X minimal inhibition concentration (MIC), 50X MIC, 10X MIC, and blank hydrogel] were 21, 13, 9, and 5 mm, respectively. In the Ti6Al4V implant biofilm model, 0.01–1% vancomycin-loaded gel exhibited significant anti-biofilm activity, measured by the MTT assay. Conclusions: Vancomycin could be loaded onto oxidized HA and adipic acid dihydrazide, which exhibited excellent drug release and in vitro antimicrobial activity with minimal cell toxicity.

Keywords

• Antibiotic hydrogel
• Vancomycin
• Biofilm