Mixed-charge pseudo-zwitterionic copolymer brush as broad spectrum antibiofilm coating

Zwitterionic polymers are classical antifouling polymers but they require specialized monomers that have cationic and anionic charges integrated into a single monomer. Herein, we show that pseudo-zwitterionic copolymers synthesized from a mixture of 2 monomers each having a single opposite polarity has excellent antibiofilm efficacy. We have discovered a new mixed-charge copolymer brush (#1-A) synthesized from 2 oppositely charged monomers, the anionic SPM (3-Sulfopropyl methacrylate) and the cationic AMPTMA ((3-Acrylamidopropyl) trimethylammonium chloride), that achieves broad spectrum in vitro antibiofilm effect of greater than 99% reductions against all six Gram-positive and Gram-negative bacteria tested. In the murine subcutaneous wound catheter infection models, the #1-A has good long-term anti-biofilm efficacy against MRSA and Pseudomonas aeruginosa of 3.41 and 3.19 orders respectively, outperforming previous mixed-charge copolymer coatings. We discovered a new method to choose the cationic/anionic pair combination to form the best antibiofilm copolymer brush coating by exploiting the solution polymerization kinetics disparity between the cationic and anionic monomers. We also showed that #1-A is softer and has higher hydration than the classical zwitterionic polymer. This study shows the possibility of achieving potent antibiofilm efficacy by combining readily available opposite singly charged monomers.Agency for Science, Technology and Research (A*STAR)Ministry of Education (MOE)Ministry of Health (MOH)Nanyang Technological UniversityAccepted versionThis research is supported by the Singapore Ministry of Education under its Singapore Ministry of Education Academic Research Fund Tier 3 grants (MOE2013-T3-1-004 and MOE2018-T3-1-003). The authors also thank the funding support from a Singapore Ministry of Health Industry Alignment Fund (NMRC/MOHIAFCAT2/003/2014), an A*STAR Industry Alignment Fund (Wound Care Innovation for the Tropics IAF-PP (HBMS Domain), H17/01/a0/0M9), an A*STAR RIE2020 Advanced Manufacturing and Engineering (AME) IAP-PP Specialty Chemicals Program (Grant No. A1786a0032) and Nanyang Technological University (NTU)