Charge-switchable polymeric coating kills bacteria and prevents biofilm formation in vivo.

Abstract

Preventing bacterial biofilm formation on medical devices and implants in vivo still remains a daunting task. Current antibacterial coatings to combat implant-associated infections are generally composed of toxic metals or non-degradable polymers and involve multistep surface modifications. Here we present a charge-switchable antibacterial and antibiofilm coating based on water-insoluble cationic hydrophobic polymers that are soluble in organic solvents and can be non-covalently coated onto different surfaces. Towards this, a library of quaternary polyethylenimine (QPEI) polymers with amide or ester group in their pendant alkyl chain was developed. These QPEIs are shown to hydrolyze from active cationic to non-toxic zwitterionic polymers under acidic or enzymatic conditions. Notably polymers with both zwitterionic and cationic groups, obtained upon incomplete hydrolysis of QPEIs, are shown to retain their antibacterial activity with much lower toxicity towards mammalian cells. Furthermore the zwitterionic polymer, fully hydrolyzed product of the QPEIs, is shown to be non-toxic to mammalian cells in vitro as well as in vivo. The QPEIs-coated surfaces are shown to kill bacteria and prevent formation of biofilm. In an in vivo mice model, the QPEIscoated medical grade catheter is shown to reduce methicillin-resistant Staphylococcus aureus (MRSA) contamination both on the catheter surface and in the adjacent tissues (99.99% reduction compared to non-coated catheter). Additionally, biofilm formation is inhibited on the catheter surface with negligible inflammation in the adjacent tissue. The above results thus highlight the importance of these polymers to be used as effective antibacterial coatings in biomedical applications.