A mathematical model of the enhanced permeability and retention effect for liposome transport in solid tumors.

The discovery of the enhanced permeability and retention (EPR) effect has resulted in the development of nanomedicines, including liposome-based formulations of drugs, as cancer therapies. The use of liposomes has resulted in substantial increases in accumulation of drugs in solid tumors; yet, signi...

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Autores principales:	Shawn Stapleton, Michael Milosevic, Christine Allen, Jinzi Zheng, Michael Dunne, Ivan Yeung, David A Jaffray
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ccdf03f2a6c44b06a1ed145eed2b6e84
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spelling	oai:doaj.org-article:ccdf03f2a6c44b06a1ed145eed2b6e842021-11-18T08:43:58ZA mathematical model of the enhanced permeability and retention effect for liposome transport in solid tumors.1932-620310.1371/journal.pone.0081157https://doaj.org/article/ccdf03f2a6c44b06a1ed145eed2b6e842013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24312530/?tool=EBIhttps://doaj.org/toc/1932-6203The discovery of the enhanced permeability and retention (EPR) effect has resulted in the development of nanomedicines, including liposome-based formulations of drugs, as cancer therapies. The use of liposomes has resulted in substantial increases in accumulation of drugs in solid tumors; yet, significant improvements in therapeutic efficacy have yet to be achieved. Imaging of the tumor accumulation of liposomes has revealed that this poor or variable performance is in part due to heterogeneous inter-subject and intra-tumoral liposome accumulation, which occurs as a result of an abnormal transport microenvironment. A mathematical model that relates liposome accumulation to the underlying transport properties in solid tumors could provide insight into inter and intra-tumoral variations in the EPR effect. In this paper, we present a theoretical framework to describe liposome transport in solid tumors. The mathematical model is based on biophysical transport equations that describe pressure driven fluid flow across blood vessels and through the tumor interstitium. The model was validated by direct comparison with computed tomography measurements of tumor accumulation of liposomes in three preclinical tumor models. The mathematical model was fit to liposome accumulation curves producing predictions of transport parameters that reflect the tumor microenvironment. Notably, all fits had a high coefficient of determination and predictions of interstitial fluid pressure agreed with previously published independent measurements made in the same tumor type. Furthermore, it was demonstrated that the model attributed inter-subject heterogeneity in liposome accumulation to variations in peak interstitial fluid pressure. These findings highlight the relationship between transvascular and interstitial flow dynamics and variations in the EPR effect. In conclusion, we have presented a theoretical framework that predicts inter-subject and intra-tumoral variations in the EPR effect based on fundamental properties of the tumor microenvironment and forms the basis for transport modeling of liposome drug delivery.Shawn StapletonMichael MilosevicChristine AllenJinzi ZhengMichael DunneIvan YeungDavid A JaffrayPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e81157 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shawn Stapleton Michael Milosevic Christine Allen Jinzi Zheng Michael Dunne Ivan Yeung David A Jaffray A mathematical model of the enhanced permeability and retention effect for liposome transport in solid tumors.
description	The discovery of the enhanced permeability and retention (EPR) effect has resulted in the development of nanomedicines, including liposome-based formulations of drugs, as cancer therapies. The use of liposomes has resulted in substantial increases in accumulation of drugs in solid tumors; yet, significant improvements in therapeutic efficacy have yet to be achieved. Imaging of the tumor accumulation of liposomes has revealed that this poor or variable performance is in part due to heterogeneous inter-subject and intra-tumoral liposome accumulation, which occurs as a result of an abnormal transport microenvironment. A mathematical model that relates liposome accumulation to the underlying transport properties in solid tumors could provide insight into inter and intra-tumoral variations in the EPR effect. In this paper, we present a theoretical framework to describe liposome transport in solid tumors. The mathematical model is based on biophysical transport equations that describe pressure driven fluid flow across blood vessels and through the tumor interstitium. The model was validated by direct comparison with computed tomography measurements of tumor accumulation of liposomes in three preclinical tumor models. The mathematical model was fit to liposome accumulation curves producing predictions of transport parameters that reflect the tumor microenvironment. Notably, all fits had a high coefficient of determination and predictions of interstitial fluid pressure agreed with previously published independent measurements made in the same tumor type. Furthermore, it was demonstrated that the model attributed inter-subject heterogeneity in liposome accumulation to variations in peak interstitial fluid pressure. These findings highlight the relationship between transvascular and interstitial flow dynamics and variations in the EPR effect. In conclusion, we have presented a theoretical framework that predicts inter-subject and intra-tumoral variations in the EPR effect based on fundamental properties of the tumor microenvironment and forms the basis for transport modeling of liposome drug delivery.
format	article
author	Shawn Stapleton Michael Milosevic Christine Allen Jinzi Zheng Michael Dunne Ivan Yeung David A Jaffray
author_facet	Shawn Stapleton Michael Milosevic Christine Allen Jinzi Zheng Michael Dunne Ivan Yeung David A Jaffray
author_sort	Shawn Stapleton
title	A mathematical model of the enhanced permeability and retention effect for liposome transport in solid tumors.
title_short	A mathematical model of the enhanced permeability and retention effect for liposome transport in solid tumors.
title_full	A mathematical model of the enhanced permeability and retention effect for liposome transport in solid tumors.
title_fullStr	A mathematical model of the enhanced permeability and retention effect for liposome transport in solid tumors.
title_full_unstemmed	A mathematical model of the enhanced permeability and retention effect for liposome transport in solid tumors.
title_sort	mathematical model of the enhanced permeability and retention effect for liposome transport in solid tumors.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/ccdf03f2a6c44b06a1ed145eed2b6e84
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A mathematical model of the enhanced permeability and retention effect for liposome transport in solid tumors.

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