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Scaling behavior of drug transport and absorption in in silico cerebral capillary networks

Drug delivery to the brain is challenging due to the presence of the blood-brain barrier. Mathematical modeling and simulation are essential tools for the deeper understanding of transport processes in the blood, across the blood-brain barrier and within the tissue. Here we present a mathematical mo...

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Detalles Bibliográficos
Autores principales: Langhoff, William, Riggs, Alexander, Hinow, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6039031/
https://www.ncbi.nlm.nih.gov/pubmed/29990324
http://dx.doi.org/10.1371/journal.pone.0200266
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author Langhoff, William
Riggs, Alexander
Hinow, Peter
author_facet Langhoff, William
Riggs, Alexander
Hinow, Peter
author_sort Langhoff, William
collection PubMed
description Drug delivery to the brain is challenging due to the presence of the blood-brain barrier. Mathematical modeling and simulation are essential tools for the deeper understanding of transport processes in the blood, across the blood-brain barrier and within the tissue. Here we present a mathematical model for drug delivery through capillary networks with increasingly complex topologies with the goal to understand the scaling behavior of model predictions on a coarse-to-fine sequence of grids. We apply our model to the delivery of L-Dopa, the primary drug used in the therapy of Parkinson’s Disease. Our model replicates observed blood flow rates and ratios between plasma and tissue concentrations. We propose an optimal network grain size for the simulation of tissue volumes of 1 cm(3) that allows to make reliable predictions with reasonable computational costs.
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spelling pubmed-60390312018-07-19 Scaling behavior of drug transport and absorption in in silico cerebral capillary networks Langhoff, William Riggs, Alexander Hinow, Peter PLoS One Research Article Drug delivery to the brain is challenging due to the presence of the blood-brain barrier. Mathematical modeling and simulation are essential tools for the deeper understanding of transport processes in the blood, across the blood-brain barrier and within the tissue. Here we present a mathematical model for drug delivery through capillary networks with increasingly complex topologies with the goal to understand the scaling behavior of model predictions on a coarse-to-fine sequence of grids. We apply our model to the delivery of L-Dopa, the primary drug used in the therapy of Parkinson’s Disease. Our model replicates observed blood flow rates and ratios between plasma and tissue concentrations. We propose an optimal network grain size for the simulation of tissue volumes of 1 cm(3) that allows to make reliable predictions with reasonable computational costs. Public Library of Science 2018-07-10 /pmc/articles/PMC6039031/ /pubmed/29990324 http://dx.doi.org/10.1371/journal.pone.0200266 Text en © 2018 Langhoff 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
Langhoff, William
Riggs, Alexander
Hinow, Peter
Scaling behavior of drug transport and absorption in in silico cerebral capillary networks
title Scaling behavior of drug transport and absorption in in silico cerebral capillary networks
title_full Scaling behavior of drug transport and absorption in in silico cerebral capillary networks
title_fullStr Scaling behavior of drug transport and absorption in in silico cerebral capillary networks
title_full_unstemmed Scaling behavior of drug transport and absorption in in silico cerebral capillary networks
title_short Scaling behavior of drug transport and absorption in in silico cerebral capillary networks
title_sort scaling behavior of drug transport and absorption in in silico cerebral capillary networks
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6039031/
https://www.ncbi.nlm.nih.gov/pubmed/29990324
http://dx.doi.org/10.1371/journal.pone.0200266
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