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Pre-Clinical Investigation of Keratose as an Excipient of Drug Coated Balloons

Background: Drug-coated balloons (DCBs), which deliver anti-proliferative drugs with the aid of excipients, have emerged as a new endovascular therapy for the treatment of peripheral arterial disease. In this study, we evaluated the use of keratose (KOS) as a novel DCB-coating excipient to deliver a...

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Autores principales: Goel, Emily, Erwin, Megan, Cawthon, Claire V., Schaff, Carson, Fedor, Nathaniel, Rayl, Trevor, Wilson, Onree, Christians, Uwe, Register, Thomas C., Geary, Randolph L., Saul, Justin, Yazdani, Saami K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180741/
https://www.ncbi.nlm.nih.gov/pubmed/32244375
http://dx.doi.org/10.3390/molecules25071596
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author Goel, Emily
Erwin, Megan
Cawthon, Claire V.
Schaff, Carson
Fedor, Nathaniel
Rayl, Trevor
Wilson, Onree
Christians, Uwe
Register, Thomas C.
Geary, Randolph L.
Saul, Justin
Yazdani, Saami K.
author_facet Goel, Emily
Erwin, Megan
Cawthon, Claire V.
Schaff, Carson
Fedor, Nathaniel
Rayl, Trevor
Wilson, Onree
Christians, Uwe
Register, Thomas C.
Geary, Randolph L.
Saul, Justin
Yazdani, Saami K.
author_sort Goel, Emily
collection PubMed
description Background: Drug-coated balloons (DCBs), which deliver anti-proliferative drugs with the aid of excipients, have emerged as a new endovascular therapy for the treatment of peripheral arterial disease. In this study, we evaluated the use of keratose (KOS) as a novel DCB-coating excipient to deliver and retain paclitaxel. Methods: A custom coating method was developed to deposit KOS and paclitaxel on uncoated angioplasty balloons. The retention of the KOS-paclitaxel coating, in comparison to a commercially available DCB, was evaluated using a novel vascular-motion simulating ex vivo flow model at 1 h and 3 days. Additionally, the locoregional biological response of the KOS-paclitaxel coating was evaluated in a rabbit ilio-femoral injury model at 14 days. Results: The KOS coating exhibited greater retention of the paclitaxel at 3 days under pulsatile conditions with vascular motion as compared to the commercially available DCB (14.89 ± 4.12 ng/mg vs. 0.60 ± 0.26 ng/mg, p = 0.018). Histological analysis of the KOS–paclitaxel-treated arteries demonstrated a significant reduction in neointimal thickness as compared to the uncoated balloons, KOS-only balloon and paclitaxel-only balloon. Conclusions: The ability to enhance drug delivery and retention in targeted arterial segments can ultimately improve clinical peripheral endovascular outcomes.
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spelling pubmed-71807412020-05-01 Pre-Clinical Investigation of Keratose as an Excipient of Drug Coated Balloons Goel, Emily Erwin, Megan Cawthon, Claire V. Schaff, Carson Fedor, Nathaniel Rayl, Trevor Wilson, Onree Christians, Uwe Register, Thomas C. Geary, Randolph L. Saul, Justin Yazdani, Saami K. Molecules Article Background: Drug-coated balloons (DCBs), which deliver anti-proliferative drugs with the aid of excipients, have emerged as a new endovascular therapy for the treatment of peripheral arterial disease. In this study, we evaluated the use of keratose (KOS) as a novel DCB-coating excipient to deliver and retain paclitaxel. Methods: A custom coating method was developed to deposit KOS and paclitaxel on uncoated angioplasty balloons. The retention of the KOS-paclitaxel coating, in comparison to a commercially available DCB, was evaluated using a novel vascular-motion simulating ex vivo flow model at 1 h and 3 days. Additionally, the locoregional biological response of the KOS-paclitaxel coating was evaluated in a rabbit ilio-femoral injury model at 14 days. Results: The KOS coating exhibited greater retention of the paclitaxel at 3 days under pulsatile conditions with vascular motion as compared to the commercially available DCB (14.89 ± 4.12 ng/mg vs. 0.60 ± 0.26 ng/mg, p = 0.018). Histological analysis of the KOS–paclitaxel-treated arteries demonstrated a significant reduction in neointimal thickness as compared to the uncoated balloons, KOS-only balloon and paclitaxel-only balloon. Conclusions: The ability to enhance drug delivery and retention in targeted arterial segments can ultimately improve clinical peripheral endovascular outcomes. MDPI 2020-03-31 /pmc/articles/PMC7180741/ /pubmed/32244375 http://dx.doi.org/10.3390/molecules25071596 Text en © 2020 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
Goel, Emily
Erwin, Megan
Cawthon, Claire V.
Schaff, Carson
Fedor, Nathaniel
Rayl, Trevor
Wilson, Onree
Christians, Uwe
Register, Thomas C.
Geary, Randolph L.
Saul, Justin
Yazdani, Saami K.
Pre-Clinical Investigation of Keratose as an Excipient of Drug Coated Balloons
title Pre-Clinical Investigation of Keratose as an Excipient of Drug Coated Balloons
title_full Pre-Clinical Investigation of Keratose as an Excipient of Drug Coated Balloons
title_fullStr Pre-Clinical Investigation of Keratose as an Excipient of Drug Coated Balloons
title_full_unstemmed Pre-Clinical Investigation of Keratose as an Excipient of Drug Coated Balloons
title_short Pre-Clinical Investigation of Keratose as an Excipient of Drug Coated Balloons
title_sort pre-clinical investigation of keratose as an excipient of drug coated balloons
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180741/
https://www.ncbi.nlm.nih.gov/pubmed/32244375
http://dx.doi.org/10.3390/molecules25071596
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