Cargando…

Effect of Relative Arrangement of Cationic and Lipophilic Moieties on Hemolytic and Antibacterial Activities of PEGylated Polyacrylates

Synthetic amphiphilic polymers have been established as potentially efficient agents to combat widespread deadly infections involving antibiotic resistant superbugs. Incorporation of poly(ethylene glycol) (PEG) side chains into amphiphilic copolymers can reduce their hemolytic activity while maintai...

Descripción completa

Detalles Bibliográficos
Autores principales: Punia, Ashish, Lee, Kevin, He, Edward, Mukherjee, Sumit, Mancuso, Andrew, Banerjee, Probal, Yang, Nan-Loh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632729/
https://www.ncbi.nlm.nih.gov/pubmed/26473831
http://dx.doi.org/10.3390/ijms161023867
_version_ 1782399082777542656
author Punia, Ashish
Lee, Kevin
He, Edward
Mukherjee, Sumit
Mancuso, Andrew
Banerjee, Probal
Yang, Nan-Loh
author_facet Punia, Ashish
Lee, Kevin
He, Edward
Mukherjee, Sumit
Mancuso, Andrew
Banerjee, Probal
Yang, Nan-Loh
author_sort Punia, Ashish
collection PubMed
description Synthetic amphiphilic polymers have been established as potentially efficient agents to combat widespread deadly infections involving antibiotic resistant superbugs. Incorporation of poly(ethylene glycol) (PEG) side chains into amphiphilic copolymers can reduce their hemolytic activity while maintaining high antibacterial activity. Our study found that the incorporation of PEG has substantially different effects on the hemolytic and antibacterial activities of copolymers depending on structural variations in the positions of cationic centers relative to hydrophobic groups. The PEG side chains dramatically reduced the hemolytic activities in copolymers with hydrophobic hexyl and cationic groups on the same repeating unit. However, in case of terpolymers with cationic and lipophilic groups placed on separate repeating units, the presence of PEG has significantly lower effect on hemolytic activities of these copolymers. PEGylated terpolymers displayed substantially lower activity against Staphylococcus aureus (S. aureus) than Escherichia coli (E. coli) suggesting the deterring effect of S. aureus’ peptidoglycan cell wall against the penetration of PEGylated polymers. Time-kill studies confirmed the bactericidal activity of these copolymers and a 5 log reduction in E. coli colony forming units was observed within 2 h of polymer treatment.
format Online
Article
Text
id pubmed-4632729
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-46327292015-11-23 Effect of Relative Arrangement of Cationic and Lipophilic Moieties on Hemolytic and Antibacterial Activities of PEGylated Polyacrylates Punia, Ashish Lee, Kevin He, Edward Mukherjee, Sumit Mancuso, Andrew Banerjee, Probal Yang, Nan-Loh Int J Mol Sci Article Synthetic amphiphilic polymers have been established as potentially efficient agents to combat widespread deadly infections involving antibiotic resistant superbugs. Incorporation of poly(ethylene glycol) (PEG) side chains into amphiphilic copolymers can reduce their hemolytic activity while maintaining high antibacterial activity. Our study found that the incorporation of PEG has substantially different effects on the hemolytic and antibacterial activities of copolymers depending on structural variations in the positions of cationic centers relative to hydrophobic groups. The PEG side chains dramatically reduced the hemolytic activities in copolymers with hydrophobic hexyl and cationic groups on the same repeating unit. However, in case of terpolymers with cationic and lipophilic groups placed on separate repeating units, the presence of PEG has significantly lower effect on hemolytic activities of these copolymers. PEGylated terpolymers displayed substantially lower activity against Staphylococcus aureus (S. aureus) than Escherichia coli (E. coli) suggesting the deterring effect of S. aureus’ peptidoglycan cell wall against the penetration of PEGylated polymers. Time-kill studies confirmed the bactericidal activity of these copolymers and a 5 log reduction in E. coli colony forming units was observed within 2 h of polymer treatment. MDPI 2015-10-09 /pmc/articles/PMC4632729/ /pubmed/26473831 http://dx.doi.org/10.3390/ijms161023867 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Punia, Ashish
Lee, Kevin
He, Edward
Mukherjee, Sumit
Mancuso, Andrew
Banerjee, Probal
Yang, Nan-Loh
Effect of Relative Arrangement of Cationic and Lipophilic Moieties on Hemolytic and Antibacterial Activities of PEGylated Polyacrylates
title Effect of Relative Arrangement of Cationic and Lipophilic Moieties on Hemolytic and Antibacterial Activities of PEGylated Polyacrylates
title_full Effect of Relative Arrangement of Cationic and Lipophilic Moieties on Hemolytic and Antibacterial Activities of PEGylated Polyacrylates
title_fullStr Effect of Relative Arrangement of Cationic and Lipophilic Moieties on Hemolytic and Antibacterial Activities of PEGylated Polyacrylates
title_full_unstemmed Effect of Relative Arrangement of Cationic and Lipophilic Moieties on Hemolytic and Antibacterial Activities of PEGylated Polyacrylates
title_short Effect of Relative Arrangement of Cationic and Lipophilic Moieties on Hemolytic and Antibacterial Activities of PEGylated Polyacrylates
title_sort effect of relative arrangement of cationic and lipophilic moieties on hemolytic and antibacterial activities of pegylated polyacrylates
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632729/
https://www.ncbi.nlm.nih.gov/pubmed/26473831
http://dx.doi.org/10.3390/ijms161023867
work_keys_str_mv AT puniaashish effectofrelativearrangementofcationicandlipophilicmoietiesonhemolyticandantibacterialactivitiesofpegylatedpolyacrylates
AT leekevin effectofrelativearrangementofcationicandlipophilicmoietiesonhemolyticandantibacterialactivitiesofpegylatedpolyacrylates
AT heedward effectofrelativearrangementofcationicandlipophilicmoietiesonhemolyticandantibacterialactivitiesofpegylatedpolyacrylates
AT mukherjeesumit effectofrelativearrangementofcationicandlipophilicmoietiesonhemolyticandantibacterialactivitiesofpegylatedpolyacrylates
AT mancusoandrew effectofrelativearrangementofcationicandlipophilicmoietiesonhemolyticandantibacterialactivitiesofpegylatedpolyacrylates
AT banerjeeprobal effectofrelativearrangementofcationicandlipophilicmoietiesonhemolyticandantibacterialactivitiesofpegylatedpolyacrylates
AT yangnanloh effectofrelativearrangementofcationicandlipophilicmoietiesonhemolyticandantibacterialactivitiesofpegylatedpolyacrylates