Development of a tumor tissue mimicking model with endothelial cell layer and collagen gel for evaluating drug penetration

Noboru Sasaki, Clemens Bos, Jean-Michel Escoffre, Gerrit Storm, Chrit Moonen

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Scopus)

Abstract

The endothelial cells of vessels, the interstitial matrix and the distance between the tumor cells and vessels, are the major penetration barriers for intravenously administered anticancer drugs in reaching tumor cells after intravenous injection. The availability of a tumor tissue-mimicking model that includes both the endothelial cell layer and the extracellular matrix would be beneficial to assess drug penetration in early stages of drug development. Here, we propose a novel in vitro model for studying the above mentioned barriers. Human umbilical vein endothelial cells were cultured as a single layer on a collagen type-I coated permeable cell culture insert. After culturing for five days, the insert was superimposed on collagen type-I gel containing cancer cells. The system was evaluated for assessing penetration-enhancement by ultrasound triggered microbubble cavitation. Our model allowed visualization of the penetration distance of a model drug (fluorescein isothiocyanate – Dextran 500000-conjugated, FD500) from the endothelial cell layer into the cancer cell containing collagen matrix upon different sonication treatments. Initial results showed that the model allows the visualization of drug penetration and that the endothelial cell layer is affecting this. The presented in vitro model aims to mimic vessels and stromal tissue in cancer, and thus can aid in the assessment of drug penetration in the case of tumor-targeted drug delivery, and in the reduction and refinement of animal studies.
Original languageUndefined
Pages (from-to)118-122
JournalInternational journal of pharmaceutics
Volume482
Issue number1-2
DOIs
Publication statusPublished - 2015

Keywords

  • METIS-315204
  • IR-99931

Cite this

Sasaki, Noboru ; Bos, Clemens ; Escoffre, Jean-Michel ; Storm, Gerrit ; Moonen, Chrit. / Development of a tumor tissue mimicking model with endothelial cell layer and collagen gel for evaluating drug penetration. In: International journal of pharmaceutics. 2015 ; Vol. 482, No. 1-2. pp. 118-122.
@article{da2a3f5a68dc47eaa5707b902d103749,
title = "Development of a tumor tissue mimicking model with endothelial cell layer and collagen gel for evaluating drug penetration",
abstract = "The endothelial cells of vessels, the interstitial matrix and the distance between the tumor cells and vessels, are the major penetration barriers for intravenously administered anticancer drugs in reaching tumor cells after intravenous injection. The availability of a tumor tissue-mimicking model that includes both the endothelial cell layer and the extracellular matrix would be beneficial to assess drug penetration in early stages of drug development. Here, we propose a novel in vitro model for studying the above mentioned barriers. Human umbilical vein endothelial cells were cultured as a single layer on a collagen type-I coated permeable cell culture insert. After culturing for five days, the insert was superimposed on collagen type-I gel containing cancer cells. The system was evaluated for assessing penetration-enhancement by ultrasound triggered microbubble cavitation. Our model allowed visualization of the penetration distance of a model drug (fluorescein isothiocyanate – Dextran 500000-conjugated, FD500) from the endothelial cell layer into the cancer cell containing collagen matrix upon different sonication treatments. Initial results showed that the model allows the visualization of drug penetration and that the endothelial cell layer is affecting this. The presented in vitro model aims to mimic vessels and stromal tissue in cancer, and thus can aid in the assessment of drug penetration in the case of tumor-targeted drug delivery, and in the reduction and refinement of animal studies.",
keywords = "METIS-315204, IR-99931",
author = "Noboru Sasaki and Clemens Bos and Jean-Michel Escoffre and Gerrit Storm and Chrit Moonen",
note = "Particulate Systems in Nanomedicine — Selected papers from a 2014 EWPS Workshop",
year = "2015",
doi = "10.1016/j.ijpharm.2015.01.039",
language = "Undefined",
volume = "482",
pages = "118--122",
journal = "International journal of pharmaceutics",
issn = "0378-5173",
publisher = "Elsevier",
number = "1-2",

}

Development of a tumor tissue mimicking model with endothelial cell layer and collagen gel for evaluating drug penetration. / Sasaki, Noboru; Bos, Clemens; Escoffre, Jean-Michel; Storm, Gerrit; Moonen, Chrit.

In: International journal of pharmaceutics, Vol. 482, No. 1-2, 2015, p. 118-122.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Development of a tumor tissue mimicking model with endothelial cell layer and collagen gel for evaluating drug penetration

AU - Sasaki, Noboru

AU - Bos, Clemens

AU - Escoffre, Jean-Michel

AU - Storm, Gerrit

AU - Moonen, Chrit

N1 - Particulate Systems in Nanomedicine — Selected papers from a 2014 EWPS Workshop

PY - 2015

Y1 - 2015

N2 - The endothelial cells of vessels, the interstitial matrix and the distance between the tumor cells and vessels, are the major penetration barriers for intravenously administered anticancer drugs in reaching tumor cells after intravenous injection. The availability of a tumor tissue-mimicking model that includes both the endothelial cell layer and the extracellular matrix would be beneficial to assess drug penetration in early stages of drug development. Here, we propose a novel in vitro model for studying the above mentioned barriers. Human umbilical vein endothelial cells were cultured as a single layer on a collagen type-I coated permeable cell culture insert. After culturing for five days, the insert was superimposed on collagen type-I gel containing cancer cells. The system was evaluated for assessing penetration-enhancement by ultrasound triggered microbubble cavitation. Our model allowed visualization of the penetration distance of a model drug (fluorescein isothiocyanate – Dextran 500000-conjugated, FD500) from the endothelial cell layer into the cancer cell containing collagen matrix upon different sonication treatments. Initial results showed that the model allows the visualization of drug penetration and that the endothelial cell layer is affecting this. The presented in vitro model aims to mimic vessels and stromal tissue in cancer, and thus can aid in the assessment of drug penetration in the case of tumor-targeted drug delivery, and in the reduction and refinement of animal studies.

AB - The endothelial cells of vessels, the interstitial matrix and the distance between the tumor cells and vessels, are the major penetration barriers for intravenously administered anticancer drugs in reaching tumor cells after intravenous injection. The availability of a tumor tissue-mimicking model that includes both the endothelial cell layer and the extracellular matrix would be beneficial to assess drug penetration in early stages of drug development. Here, we propose a novel in vitro model for studying the above mentioned barriers. Human umbilical vein endothelial cells were cultured as a single layer on a collagen type-I coated permeable cell culture insert. After culturing for five days, the insert was superimposed on collagen type-I gel containing cancer cells. The system was evaluated for assessing penetration-enhancement by ultrasound triggered microbubble cavitation. Our model allowed visualization of the penetration distance of a model drug (fluorescein isothiocyanate – Dextran 500000-conjugated, FD500) from the endothelial cell layer into the cancer cell containing collagen matrix upon different sonication treatments. Initial results showed that the model allows the visualization of drug penetration and that the endothelial cell layer is affecting this. The presented in vitro model aims to mimic vessels and stromal tissue in cancer, and thus can aid in the assessment of drug penetration in the case of tumor-targeted drug delivery, and in the reduction and refinement of animal studies.

KW - METIS-315204

KW - IR-99931

U2 - 10.1016/j.ijpharm.2015.01.039

DO - 10.1016/j.ijpharm.2015.01.039

M3 - Article

VL - 482

SP - 118

EP - 122

JO - International journal of pharmaceutics

JF - International journal of pharmaceutics

SN - 0378-5173

IS - 1-2

ER -