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Tuning the Selectivity of Biodegradable Antimicrobial Cationic Polycarbonates by Exchanging the Counter-Anion.

Abstract
There is a growing interest in modern healthcare to develop systems able to fight antibiotic resistant bacteria. Antimicrobial cationic biodegradable polymers able to mimic antimicrobial peptides have shown to be effective against both Gram-positive and Gram-negative bacteria. In these systems, the hydrophilic-hydrophobic ratio and the cationic charge density play a pivotal role in defining the killing efficiency. Nevertheless, many of these antimicrobial polymers show relatively low selectivity as defined by the relative toxicity to mammalian cells or hemolysis relative to pathogens. In this study, a series of polycarbonates containing pendant quaternary ammoniums are used to understand the role of different counter-anions including chloride, citrate, malonate, benzoate, acetate, lactate and trifluoroacetate, and the antibiotic penicillin on antimicrobial efficacy and selectivity. Interestingly, it is found that in spite of the strong antimicrobial activity of trifluoroacetate and benzoate anions, they prove to be much less hemolytic than chloride anion. It is believed that the proper selection of the anion could enhance the potential of antimicrobial polymers to fight against clinically relevant pathogenic infections, while concurrently mitigating harmful side effects.
AuthorsMehmet Isik, Jeremy P K Tan, Robert J Ono, Ana Sanchez-Sanchez, David Mecerreyes, Yi Yan Yang, James L Hedrick, Haritz Sardon
JournalMacromolecular bioscience (Macromol Biosci) Vol. 16 Issue 9 Pg. 1360-7 (09 2016) ISSN: 1616-5195 [Electronic] Germany
PMID27273254 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Chemical References
  • Anions
  • Anti-Infective Agents
  • Biocompatible Materials
  • Cations
  • Polycarboxylate Cement
  • polycarbonate
Topics
  • Animals
  • Anions
  • Anti-Infective Agents (pharmacology)
  • Bacteria (drug effects)
  • Biocompatible Materials (pharmacology)
  • Cations
  • Fungi (drug effects)
  • Hemolysis (drug effects)
  • Humans
  • Ion Exchange
  • Microbial Sensitivity Tests
  • Polycarboxylate Cement (chemical synthesis, chemistry, pharmacology)
  • Proton Magnetic Resonance Spectroscopy
  • Rats
  • Spectroscopy, Fourier Transform Infrared

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