Broad Spectrum Macromolecular Antimicrobials with Biofilm Disruption Capability and In Vivo Efficacy. Issue 16 (15th May 2017)

• Record Type: Journal Article
• Authors: Tan, Jeremy P. K.; Coady, Daniel J.; Sardon, Haritz; Yuen, Alexander; Gao, Shujun; Lim, Shaun W.; Liang, Zhen Chang; Tan, Eddy W.; Venkataraman, Shrinivas; Engler, Amanda C.; Fevre, Mareva; Ono, Robert; Yang, Yi Yan; Hedrick, James L.
• Is Part Of: Advanced healthcare materials. Volume 6:Issue 16(2017)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-05-15
• Subjects: antibiofilms -- antimicrobial -- eight‐membered polycarbonates -- in vivo antimicrobial activity -- membrane‐lytic; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1002/adhm.201601420
• Languages: English
• ISSNs: 2192-2640

Abstract

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 activity with fast killing kinetics, and in vivo antimicrobial activity make these macromolecular antimicrobials ideal candidates for prevention of sepsis and treatment of infections. Abstract : Biodegradable eight membered polycarbonates that exhibit broad spectrum antimicrobial activity are synthesized by organocatalytic ring‐opening polymerization. These materials are nonhemolytic and nontoxic with the ability to lyse individual microbes or biofilm via membrane lytic mechanism. In a blood stream infection mouse model, the polymer, injected intravenously, removes bacteria from the blood more rapidly than the antibiotic Augmentin without causing toxicity.