Broad Spectrum Macromolecular Antimicrobials with Biofilm Disruption Capability and In Vivo Efficacy

Advanced Healthcare Materials
Jeremy P K TanJames L Hedrick

Abstract

In this study, antimicrobial polymers are synthesized by the organocatalytic ring-opening polymerization of an eight-membered heterocyclic carbonate monomer that is subsequently quaternized with methyl iodide. These polymers demonstrate activity against clinically relevant Gram-positive Staphylococcus epidermidis and Staphylococcus aureus, Gram-negative Escherichia coli and Pseudomonas aeruginosa, and fungus Candida albicans with fast killing kinetics. Importantly, the polymer efficiently inhibits biofilm growth and lyses existing biofilm, leading to a reduction in biomass and cell viability. In addition, the macromolecular antimicrobial is less likely to induce resistance as it acts via a membrane-lytic mechanism. The polymer is not cytotoxic toward mammalian cells with LD50 of 99.0 ± 11.6 mg kg-1 in mice through i.v. injection. In an S. aureus blood stream infection mouse model, the polymer removes bacteria from the blood more rapidly than the antibiotic Augmentin. At the effective dose, the polymer treatment does not damage liver and kidney tissues or functions. In addition, blood electrolyte balance remains unchanged after the treatment. The low cost of starting materials, ease of synthesis, nontoxicity, broad spectrum acti...Continue Reading

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Citations

Sep 18, 2018·Chemical Society Reviews·Greta Becker, Frederik R Wurm
May 14, 2018·Polymer Chemistry·Shrinivas VenkataramanYi Yan Yang
Nov 28, 2020·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Yanliang DongAnjie Dong
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Jun 17, 2021·Journal of the American Chemical Society·Apoorva VishwakarmaAbraham Joy
Jan 15, 2020·ACS Applied Materials & Interfaces·Jianghua LiMary B Chan-Park

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