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 nondegradable 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 noncovalently coated onto different surfaces. Toward this, a library of quaternary polyethylenimine (QPEI) polymers with an amide or ester group in their pendant alkyl chain was developed. These QPEIs are shown to hydrolyze from active cationic to nontoxic zwitterionic polymers under acidic or enzymatic conditions. Notably, polymers with both zwitterionic and cationic groups, obtained upon partial hydrolysis of QPEIs, are shown to retain their antibacterial activity with much lower toxicity toward mammalian cells. Furthermore, the zwitterionic polymer, a fully hydrolyzed product of the QPEIs, is shown to be nontoxic to mammalian cells in vitro as well as in vivo. The QPEIs, when coated onto surfaces, kill bacteria and prevent formation of biofilms. In an in vivo mice model, the QPEI-coated medical grade catheter is shown to reduce methicillin-resistant Staphylococcus aureus contamination both on the catheter surface and in the adjacent tissues (99.99% reduction compared to a noncoated 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.

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