Thermosensitive injectable dual drug-loaded chitosan-based hybrid hydrogel for treatment of orthopedic implant infections

A myriad of therapeutic agents and drug delivery systems are available to the surgeons for treating orthopedic implant-associated infections (OIAI), but only very few have demonstrated their effectiveness in preventing bacteria colonization and biofilm formation due to challenges in the local and sustainable therapeutic release. To address this issue, in this work, a thermosensitive injectable hydrogel based on chitosan (CH)-integrated hydroxyapatite nanoparticles (HAP NPs) containing vancomycin (Van) and quercetin (QC)-loaded in F127 micelles (CH-HAP-FQ-Van hydrogel) was fabricated with potential application in the treatment of OIAI. This dual drug delivery system demonstrated a pH-sensitive drug release pattern. In addition, 100 % growth inhibition of Staphylococcus aureus for a duration of 14 days was observed. Apart from the strong antioxidant activities owing to the co-administration of QC even after 432 h, this composite hydrogel revealed 95.88 ± 2.8 % S. aureus biofilm eradication. By consideration of degradation stability (53.52 ± 4.24 %) during 60 days along with smart gelation within 10 min at 37 °C and easy injectability, CH-HAP-FQ-Van hydrogel could be used as a promising ideal local drug delivery system for implant-related infections.