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Antibacterial and Antifungal Activities of Poloxamer Micelles Containing Ceragenin CSA-131 on Ciliated Tissues

Ceragenins were designed as non-peptide mimics of endogenous antimicrobial peptides, and they display broad-spectrum antibacterial and antifungal activities, including the ability to eradicate established biofilms. These features of ceragenins make them attractive potential therapeutics for persiste...

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Autores principales: Hashemi, Marjan M., Holden, Brett S., Taylor, Maddison F., Wilson, John, Coburn, Jordan, Hilton, Brian, Nance, Tania, Gubler, Shawn, Genberg, Carl, Deng, Shenglou, Savage, Paul B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6017798/
https://www.ncbi.nlm.nih.gov/pubmed/29518893
http://dx.doi.org/10.3390/molecules23030596
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author Hashemi, Marjan M.
Holden, Brett S.
Taylor, Maddison F.
Wilson, John
Coburn, Jordan
Hilton, Brian
Nance, Tania
Gubler, Shawn
Genberg, Carl
Deng, Shenglou
Savage, Paul B.
author_facet Hashemi, Marjan M.
Holden, Brett S.
Taylor, Maddison F.
Wilson, John
Coburn, Jordan
Hilton, Brian
Nance, Tania
Gubler, Shawn
Genberg, Carl
Deng, Shenglou
Savage, Paul B.
author_sort Hashemi, Marjan M.
collection PubMed
description Ceragenins were designed as non-peptide mimics of endogenous antimicrobial peptides, and they display broad-spectrum antibacterial and antifungal activities, including the ability to eradicate established biofilms. These features of ceragenins make them attractive potential therapeutics for persistent infections in the lung, including those associated with cystic fibrosis. A characteristic of an optimal therapeutic for use in the lungs and trachea is the exertion of potent antimicrobial activities without damaging the cilia that play a critical role in these tissues. In previous work, potent antimicrobial activities of ceragenin CSA-131 have been reported; however, we found in ex vivo studies that this ceragenin, at concentrations necessary to eradicate established biofilms, also causes loss of cilia function. By formulating CSA-131 in poloxamer micelles, cilia damage was eliminated and antimicrobial activity was unaffected. The ability of CSA-131, formulated with a poloxamer, to reduce the populations of fungal pathogens in tracheal and lung tissue was also observed in ex vivo studies. These findings suggest that CSA-131, formulated in micelles, may act as a potential therapeutic for polymicrobial and biofilm-related infections in the lung and trachea.
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spelling pubmed-60177982018-11-13 Antibacterial and Antifungal Activities of Poloxamer Micelles Containing Ceragenin CSA-131 on Ciliated Tissues Hashemi, Marjan M. Holden, Brett S. Taylor, Maddison F. Wilson, John Coburn, Jordan Hilton, Brian Nance, Tania Gubler, Shawn Genberg, Carl Deng, Shenglou Savage, Paul B. Molecules Article Ceragenins were designed as non-peptide mimics of endogenous antimicrobial peptides, and they display broad-spectrum antibacterial and antifungal activities, including the ability to eradicate established biofilms. These features of ceragenins make them attractive potential therapeutics for persistent infections in the lung, including those associated with cystic fibrosis. A characteristic of an optimal therapeutic for use in the lungs and trachea is the exertion of potent antimicrobial activities without damaging the cilia that play a critical role in these tissues. In previous work, potent antimicrobial activities of ceragenin CSA-131 have been reported; however, we found in ex vivo studies that this ceragenin, at concentrations necessary to eradicate established biofilms, also causes loss of cilia function. By formulating CSA-131 in poloxamer micelles, cilia damage was eliminated and antimicrobial activity was unaffected. The ability of CSA-131, formulated with a poloxamer, to reduce the populations of fungal pathogens in tracheal and lung tissue was also observed in ex vivo studies. These findings suggest that CSA-131, formulated in micelles, may act as a potential therapeutic for polymicrobial and biofilm-related infections in the lung and trachea. MDPI 2018-03-07 /pmc/articles/PMC6017798/ /pubmed/29518893 http://dx.doi.org/10.3390/molecules23030596 Text en © 2018 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 (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hashemi, Marjan M.
Holden, Brett S.
Taylor, Maddison F.
Wilson, John
Coburn, Jordan
Hilton, Brian
Nance, Tania
Gubler, Shawn
Genberg, Carl
Deng, Shenglou
Savage, Paul B.
Antibacterial and Antifungal Activities of Poloxamer Micelles Containing Ceragenin CSA-131 on Ciliated Tissues
title Antibacterial and Antifungal Activities of Poloxamer Micelles Containing Ceragenin CSA-131 on Ciliated Tissues
title_full Antibacterial and Antifungal Activities of Poloxamer Micelles Containing Ceragenin CSA-131 on Ciliated Tissues
title_fullStr Antibacterial and Antifungal Activities of Poloxamer Micelles Containing Ceragenin CSA-131 on Ciliated Tissues
title_full_unstemmed Antibacterial and Antifungal Activities of Poloxamer Micelles Containing Ceragenin CSA-131 on Ciliated Tissues
title_short Antibacterial and Antifungal Activities of Poloxamer Micelles Containing Ceragenin CSA-131 on Ciliated Tissues
title_sort antibacterial and antifungal activities of poloxamer micelles containing ceragenin csa-131 on ciliated tissues
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6017798/
https://www.ncbi.nlm.nih.gov/pubmed/29518893
http://dx.doi.org/10.3390/molecules23030596
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