Tuning the Selectivity of Biodegradable Antimicrobial Cationic Polycarbonates by Exchanging the Counter-Anion.
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.
POLYMAT, University of the Basque Country UPV/EHU Joxe Mari Korta Center, Avda. Tolosa 72, 20018, Donostia-San, Sebastián, Spain.
Mehmet
M
Isik
Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, Singapore, 138669, Singapore.
Jeremy P K
JP
Tan
IBM Almaden Research Center, 650 Harry Road, San Jose, CA, 95120, USA.
Robert J
RJ
Ono
POLYMAT, University of the Basque Country UPV/EHU Joxe Mari Korta Center, Avda. Tolosa 72, 20018, Donostia-San, Sebastián, Spain.
Ana
A
Sanchez-Sanchez
POLYMAT, University of the Basque Country UPV/EHU Joxe Mari Korta Center, Avda. Tolosa 72, 20018, Donostia-San, Sebastián, Spain.|Ikerbasque, Basque Foundation for Science, E-48011, Bilbao, Spain.
David
D
Mecerreyes
Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, Singapore, 138669, Singapore.
Yi Yan
YY
Yang
IBM Almaden Research Center, 650 Harry Road, San Jose, CA, 95120, USA.
James L
JL
Hedrick
POLYMAT, University of the Basque Country UPV/EHU Joxe Mari Korta Center, Avda. Tolosa 72, 20018, Donostia-San, Sebastián, Spain. haritz.sardon@ehu.es.
Haritz
H
Sardon
D000818:Animals; D000838:Anions; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D001672:Biocompatible Materials / Q000494:pharmacology*; D002412:Cations; D005658:Fungi / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007474:Ion Exchange; D008826:Microbial Sensitivity Tests; D011076:Polycarboxylate Cement / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D066244:Proton Magnetic Resonance Spectroscopy; D051381:Rats; D017550:Spectroscopy, Fourier Transform Infrared
D000838:Anions; D000890:Anti-Infective Agents; D001672:Biocompatible Materials; D002412:Cations; D011076:Polycarboxylate Cement; C005506:polycarbonate
anion exchange; antimicrobial; organocatalysis; polycarbonates; selective