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Optimization of Drug Delivery by Drug-Eluting Stents

Drug-eluting stents (DES), which release anti-proliferative drugs into the arterial wall in a controlled manner, have drastically reduced the rate of in-stent restenosis and revolutionized the treatment of atherosclerosis. However, late stent thrombosis remains a safety concern in DES, mainly due to...

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Autores principales: Bozsak, Franz, Gonzalez-Rodriguez, David, Sternberger, Zachary, Belitz, Paul, Bewley, Thomas, Chomaz, Jean-Marc, Barakat, Abdul I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4470631/
https://www.ncbi.nlm.nih.gov/pubmed/26083626
http://dx.doi.org/10.1371/journal.pone.0130182
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author Bozsak, Franz
Gonzalez-Rodriguez, David
Sternberger, Zachary
Belitz, Paul
Bewley, Thomas
Chomaz, Jean-Marc
Barakat, Abdul I.
author_facet Bozsak, Franz
Gonzalez-Rodriguez, David
Sternberger, Zachary
Belitz, Paul
Bewley, Thomas
Chomaz, Jean-Marc
Barakat, Abdul I.
author_sort Bozsak, Franz
collection PubMed
description Drug-eluting stents (DES), which release anti-proliferative drugs into the arterial wall in a controlled manner, have drastically reduced the rate of in-stent restenosis and revolutionized the treatment of atherosclerosis. However, late stent thrombosis remains a safety concern in DES, mainly due to delayed healing of the endothelial wound inflicted during DES implantation. We present a framework to optimize DES design such that restenosis is inhibited without affecting the endothelial healing process. To this end, we have developed a computational model of fluid flow and drug transport in stented arteries and have used this model to establish a metric for quantifying DES performance. The model takes into account the multi-layered structure of the arterial wall and incorporates a reversible binding model to describe drug interaction with the cells of the arterial wall. The model is coupled to a novel optimization algorithm that allows identification of optimal DES designs. We show that optimizing the period of drug release from DES and the initial drug concentration within the coating has a drastic effect on DES performance. Paclitaxel-eluting stents perform optimally by releasing their drug either very rapidly (within a few hours) or very slowly (over periods of several months up to one year) at concentrations considerably lower than current DES. In contrast, sirolimus-eluting stents perform optimally only when drug release is slow. The results offer explanations for recent trends in the development of DES and demonstrate the potential for large improvements in DES design relative to the current state of commercial devices.
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spelling pubmed-44706312015-06-29 Optimization of Drug Delivery by Drug-Eluting Stents Bozsak, Franz Gonzalez-Rodriguez, David Sternberger, Zachary Belitz, Paul Bewley, Thomas Chomaz, Jean-Marc Barakat, Abdul I. PLoS One Research Article Drug-eluting stents (DES), which release anti-proliferative drugs into the arterial wall in a controlled manner, have drastically reduced the rate of in-stent restenosis and revolutionized the treatment of atherosclerosis. However, late stent thrombosis remains a safety concern in DES, mainly due to delayed healing of the endothelial wound inflicted during DES implantation. We present a framework to optimize DES design such that restenosis is inhibited without affecting the endothelial healing process. To this end, we have developed a computational model of fluid flow and drug transport in stented arteries and have used this model to establish a metric for quantifying DES performance. The model takes into account the multi-layered structure of the arterial wall and incorporates a reversible binding model to describe drug interaction with the cells of the arterial wall. The model is coupled to a novel optimization algorithm that allows identification of optimal DES designs. We show that optimizing the period of drug release from DES and the initial drug concentration within the coating has a drastic effect on DES performance. Paclitaxel-eluting stents perform optimally by releasing their drug either very rapidly (within a few hours) or very slowly (over periods of several months up to one year) at concentrations considerably lower than current DES. In contrast, sirolimus-eluting stents perform optimally only when drug release is slow. The results offer explanations for recent trends in the development of DES and demonstrate the potential for large improvements in DES design relative to the current state of commercial devices. Public Library of Science 2015-06-17 /pmc/articles/PMC4470631/ /pubmed/26083626 http://dx.doi.org/10.1371/journal.pone.0130182 Text en © 2015 Bozsak 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Bozsak, Franz
Gonzalez-Rodriguez, David
Sternberger, Zachary
Belitz, Paul
Bewley, Thomas
Chomaz, Jean-Marc
Barakat, Abdul I.
Optimization of Drug Delivery by Drug-Eluting Stents
title Optimization of Drug Delivery by Drug-Eluting Stents
title_full Optimization of Drug Delivery by Drug-Eluting Stents
title_fullStr Optimization of Drug Delivery by Drug-Eluting Stents
title_full_unstemmed Optimization of Drug Delivery by Drug-Eluting Stents
title_short Optimization of Drug Delivery by Drug-Eluting Stents
title_sort optimization of drug delivery by drug-eluting stents
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4470631/
https://www.ncbi.nlm.nih.gov/pubmed/26083626
http://dx.doi.org/10.1371/journal.pone.0130182
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