Cargando…
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...
Autores principales: | , , , , , , , , , , |
---|---|
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 |
_version_ | 1783334828076171264 |
---|---|
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. |
format | Online Article Text |
id | pubmed-6017798 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT hashemimarjanm antibacterialandantifungalactivitiesofpoloxamermicellescontainingceragenincsa131onciliatedtissues AT holdenbretts antibacterialandantifungalactivitiesofpoloxamermicellescontainingceragenincsa131onciliatedtissues AT taylormaddisonf antibacterialandantifungalactivitiesofpoloxamermicellescontainingceragenincsa131onciliatedtissues AT wilsonjohn antibacterialandantifungalactivitiesofpoloxamermicellescontainingceragenincsa131onciliatedtissues AT coburnjordan antibacterialandantifungalactivitiesofpoloxamermicellescontainingceragenincsa131onciliatedtissues AT hiltonbrian antibacterialandantifungalactivitiesofpoloxamermicellescontainingceragenincsa131onciliatedtissues AT nancetania antibacterialandantifungalactivitiesofpoloxamermicellescontainingceragenincsa131onciliatedtissues AT gublershawn antibacterialandantifungalactivitiesofpoloxamermicellescontainingceragenincsa131onciliatedtissues AT genbergcarl antibacterialandantifungalactivitiesofpoloxamermicellescontainingceragenincsa131onciliatedtissues AT dengshenglou antibacterialandantifungalactivitiesofpoloxamermicellescontainingceragenincsa131onciliatedtissues AT savagepaulb antibacterialandantifungalactivitiesofpoloxamermicellescontainingceragenincsa131onciliatedtissues |