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

Abstract

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. 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). The average release percentage of vancomycin on day 3 was about 86%. The antibiotic-loaded gel was biocompatible with mesenchymal stem cell, MC3T3, and L929cell lines. The invitro inhibition zones of vancomycin-loaded hydrogel [500X minimal inhibition concentration (MIC), 50X MIC, 10X MIC, and blank hydrogel] were 21, 13, 9, and 5mm, respectively. In the Ti6Al4V implant biofilm model, 0.01-1% vancomycin-loaded gel exhibited significant anti-biofilm activity, measured by the MTT assay. Vancomycin could be loaded onto oxidized HA and adipic acid dihydrazide, which exhibited excellent drug release and invitro antimicrobial activity with minimal cell toxicity.