Background: Surgical site infection is the most common postoperative complication, affecting up to 22% of surgical procedures and is mainly caused by S. aureus and S. epidermidis. Standard treatment with systemic antibiotics frequently fails due to the rise of antibiotics resistance and the formation of biofilms, leading to clinical complications and increased healthcare costs. Therefore, more effective antibacterial treatments for surgical site infections are a major unmet need.
Aim: To develop a novel thermosensitive gel with embedded antibacterial nanoparticles for inhibition of staphylococci biofilms.
Methods: Nanoparticles comprising diethyldithiocarbamate and copper ions (DDC-Cu-NP) were produced and tested in vitro for their antibiofilm activity against methicillin resistant S. aureus (MRSA) and S. epidermidis via the AlamarBlue assay. In vivo toxicity and efficacy of the DDC-Cu-NP were investigated in infected Galleria mellonella larvae over 4 days. DDC-Cu-NP were embedded in a thermosensitive gel and prevention of biofilm growth was determined via the colony biofilm assay. Statistical analysis: log-rank test with Holm-Bonferroni adjustment of Kaplan-Meier survival curves.
Results: Treatment with DDC-Cu-NP resulted in 91% MRSA and 83% S. epidermidis biofilm killing. DDC-Cu-NP showed no toxicity in Galleria mellonella larvae and significantly increased the survival of S. epidermidis-infected larvae over 4 days (77% survival of infected, treated larvae vs. 27% survival of infected, untreated larvae, p<0.01). In the colony biofilm model, MRSA formed biofilms when left untreated, or when treated with the blank gel, while no biofilm was formed in the presence of the gel with DDC-Cu-NP.
Conclusion: The results suggest that DDC-Cu-NP are a promising antibiofilm strategy against staphylococci. Prevention of biofilm formation can be achieved locally at the surgical site by delivering DDC-Cu-NP in a thermosensitive gel. A mammalian animal study to investigate efficacy and safety of the gel is warranted.