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Polymer-assisted intratumoral delivery of ethanol: Preclinical investigation of safety and efficacy in a murine breast cancer model

Focal tumor ablation with ethanol could provide benefits in low-resource settings because of its low overall cost, minimal imaging technology requirements, and acceptable clinical outcomes. Unfortunately, ethanol ablation is not commonly utilized because of a lack of predictability of the ablation z...

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Autores principales: Nief, Corrine, Morhard, Robert, Chelales, Erika, Adrianzen Alvarez, Daniel, Bourla BS, Ioanna, Lam, Christopher T., Sag, Alan A., Crouch, Brian T., Mueller, Jenna L., Katz, David, Dewhirst, Mark W., Everitt, Jeffrey I., Ramanujam, Nirmala
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843014/
https://www.ncbi.nlm.nih.gov/pubmed/33507942
http://dx.doi.org/10.1371/journal.pone.0234535
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author Nief, Corrine
Morhard, Robert
Chelales, Erika
Adrianzen Alvarez, Daniel
Bourla BS, Ioanna
Lam, Christopher T.
Sag, Alan A.
Crouch, Brian T.
Mueller, Jenna L.
Katz, David
Dewhirst, Mark W.
Everitt, Jeffrey I.
Ramanujam, Nirmala
author_facet Nief, Corrine
Morhard, Robert
Chelales, Erika
Adrianzen Alvarez, Daniel
Bourla BS, Ioanna
Lam, Christopher T.
Sag, Alan A.
Crouch, Brian T.
Mueller, Jenna L.
Katz, David
Dewhirst, Mark W.
Everitt, Jeffrey I.
Ramanujam, Nirmala
author_sort Nief, Corrine
collection PubMed
description Focal tumor ablation with ethanol could provide benefits in low-resource settings because of its low overall cost, minimal imaging technology requirements, and acceptable clinical outcomes. Unfortunately, ethanol ablation is not commonly utilized because of a lack of predictability of the ablation zone, caused by inefficient retention of ethanol at the injection site. To create a predictable zone of ablation, we have developed a polymer-assisted ablation method using ethyl cellulose (EC) mixed with ethanol. EC is ethanol-soluble and water-insoluble, allowing for EC-ethanol to be injected as a liquid and precipitate into a solid, occluding the leakage of ethanol upon contact with tissue. The aims of this study were to compare the 1) safety, 2) release kinetics, 3) spatial distribution, 4) necrotic volume, and 5) overall survival of EC-ethanol to conventional ethanol ablation in a murine breast tumor model. Non-target tissue damage was monitored through localized adverse events recording, ethanol release kinetics with Raman spectroscopy, injectate distribution with in vivo imaging, target-tissue necrosis with NADH-diaphorase staining, and overall survival by proxy of tumor growth. EC-ethanol exhibited decreased localized adverse events, a slowing of the release rate of ethanol, more compact injection zones, 5-fold increase in target-tissue necrosis, and longer overall survival rates compared to the same volume of pure ethanol. A single 150 μL dose of 6% EC-ethanol achieved a similar survival probability rates to six daily 50 μL doses of pure ethanol used to simulate a slow-release of ethanol over 6 days. Taken together, these results demonstrate that EC-ethanol is safer and more effective than ethanol alone for ablating tumors.
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spelling pubmed-78430142021-02-04 Polymer-assisted intratumoral delivery of ethanol: Preclinical investigation of safety and efficacy in a murine breast cancer model Nief, Corrine Morhard, Robert Chelales, Erika Adrianzen Alvarez, Daniel Bourla BS, Ioanna Lam, Christopher T. Sag, Alan A. Crouch, Brian T. Mueller, Jenna L. Katz, David Dewhirst, Mark W. Everitt, Jeffrey I. Ramanujam, Nirmala PLoS One Research Article Focal tumor ablation with ethanol could provide benefits in low-resource settings because of its low overall cost, minimal imaging technology requirements, and acceptable clinical outcomes. Unfortunately, ethanol ablation is not commonly utilized because of a lack of predictability of the ablation zone, caused by inefficient retention of ethanol at the injection site. To create a predictable zone of ablation, we have developed a polymer-assisted ablation method using ethyl cellulose (EC) mixed with ethanol. EC is ethanol-soluble and water-insoluble, allowing for EC-ethanol to be injected as a liquid and precipitate into a solid, occluding the leakage of ethanol upon contact with tissue. The aims of this study were to compare the 1) safety, 2) release kinetics, 3) spatial distribution, 4) necrotic volume, and 5) overall survival of EC-ethanol to conventional ethanol ablation in a murine breast tumor model. Non-target tissue damage was monitored through localized adverse events recording, ethanol release kinetics with Raman spectroscopy, injectate distribution with in vivo imaging, target-tissue necrosis with NADH-diaphorase staining, and overall survival by proxy of tumor growth. EC-ethanol exhibited decreased localized adverse events, a slowing of the release rate of ethanol, more compact injection zones, 5-fold increase in target-tissue necrosis, and longer overall survival rates compared to the same volume of pure ethanol. A single 150 μL dose of 6% EC-ethanol achieved a similar survival probability rates to six daily 50 μL doses of pure ethanol used to simulate a slow-release of ethanol over 6 days. Taken together, these results demonstrate that EC-ethanol is safer and more effective than ethanol alone for ablating tumors. Public Library of Science 2021-01-28 /pmc/articles/PMC7843014/ /pubmed/33507942 http://dx.doi.org/10.1371/journal.pone.0234535 Text en © 2021 Nief et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Nief, Corrine
Morhard, Robert
Chelales, Erika
Adrianzen Alvarez, Daniel
Bourla BS, Ioanna
Lam, Christopher T.
Sag, Alan A.
Crouch, Brian T.
Mueller, Jenna L.
Katz, David
Dewhirst, Mark W.
Everitt, Jeffrey I.
Ramanujam, Nirmala
Polymer-assisted intratumoral delivery of ethanol: Preclinical investigation of safety and efficacy in a murine breast cancer model
title Polymer-assisted intratumoral delivery of ethanol: Preclinical investigation of safety and efficacy in a murine breast cancer model
title_full Polymer-assisted intratumoral delivery of ethanol: Preclinical investigation of safety and efficacy in a murine breast cancer model
title_fullStr Polymer-assisted intratumoral delivery of ethanol: Preclinical investigation of safety and efficacy in a murine breast cancer model
title_full_unstemmed Polymer-assisted intratumoral delivery of ethanol: Preclinical investigation of safety and efficacy in a murine breast cancer model
title_short Polymer-assisted intratumoral delivery of ethanol: Preclinical investigation of safety and efficacy in a murine breast cancer model
title_sort polymer-assisted intratumoral delivery of ethanol: preclinical investigation of safety and efficacy in a murine breast cancer model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843014/
https://www.ncbi.nlm.nih.gov/pubmed/33507942
http://dx.doi.org/10.1371/journal.pone.0234535
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