Antimicrobial resistance have become a global threat to human health with increasing incidents of superbug infections leading to burgeoning medical related costs and loss of patient lives. New antimicrobial agents based on synthetic amphiphilic polymers, mimicking the natural antimicrobial peptides, are known to disrupt bacterial cell surface via non-specific columbic and hydrophobic interactions. However, one of the challenges hindering therapeutic applications of synthetic amphiphilic polymers is the non-selective cell surface disruption activity leading to toxicity against human or mammalian cells. In this study, we investigated a combinatorial strategy to synergistically utilize high antimicrobial activity resulting from long 6-carbon space arms (distance from polymer backbone to cationic center) and separate center design with segregated lipophilic side groups and cationic centers on separate repeating units. Incorporation of shorter 2-carbon spacer arm repeating arms was employed to mitigate the high hemolytic activity arising from both 6-carbon spacer arms and alkyl side groups. Resulting copolymers with controlled incorporation of comonomer units displayed highly selective (bacteria over red blood cells) antimicrobial activity. Time dependent killing efficiency studies demonstrated that rapid bactericidal activity with 5 log reduction in bacterial (<i>Escherichia coli and Staphylococcus aureus</i>) colony forming units was achieved within two hours of polymer treatment. Bacterial surface disruption mode of antimicrobial activity was confirmed through electron microscopy analysis. These results show that a macromolecular design with combination of control of spacer arm lengths and separate center inclusion of lipophilic side groups can lead to highly selective antimicrobial polymers.<br/>

Bactericidal and non-hemolytic macromolecules through synergistic variation in spacer arm and separate center design

253rd National Meeting (2017)

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