A novel in vitro permeability assay using three-dimensional cell culture system

Jong Bong Lee; Sung Hwa Son; Min Chul Park; Tae Hwan Kim; Min Gi Kim; Sun Dong Yoo; Sunghoon Kim

doi:10.1016/j.jbiotec.2014.12.019

A novel in vitro permeability assay using three-dimensional cell culture system

Jong Bong Lee, Sung Hwa Son, Min Chul Park, Tae Hwan Kim, Min Gi Kim, Sun Dong Yoo, Sunghoon Kim

Department of Pharmacy

Research output: Contribution to journal › Article › peer-review

10 Citations (Scopus)

Abstract

Three-dimensional (3D) cell culture systems are well-known to better represent the in vivo environment and they are applied to many areas of research. Spheroid model is one of the systems of 3D cell culture and here in our research, a permeability assay utilizing the spheroids was developed. Number of cells forming the spheroids, initial compound concentration, and incubation time were optimized to provide the best assay performance. After development of the assay, it was evaluated with 22 commercially available compounds. The developed Caco-2 3D spheroid permeability assay demonstrated a reasonable correlation with human absorption values. The parallel artificial membrane permeability assay (PAMPA) was also performed for the same set of compounds and the results were compared with those of the 3D permeability assay. The correlation with human absorption values was shown to be improved with the 3D permeability assay. The successful development of the Caco-2 3D spheroid permeability assay also suggests the potential application of the 3D cell culture systems to other areas of pharmacokinetic research.

Original language	English
Pages (from-to)	93-100
Number of pages	8
Journal	Journal of Biotechnology
Volume	205
DOIs	https://doi.org/10.1016/j.jbiotec.2014.12.019
Publication status	Published - 2015 Jul 10

Bibliographical note

Funding Information:
This work was supported by the Global Frontier Project (grants NRF-M3A6A4-2010-0029785 ) of National Research Foundation funded by the Ministry of Science, ICT & Future Planning (MSIP) of Korea. This work was also supported by a grant from Gyeonggi Research Development Program .

Publisher Copyright:
© 2015 Elsevier B.V.

All Science Journal Classification (ASJC) codes

Biotechnology
Bioengineering
Applied Microbiology and Biotechnology

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10.1016/j.jbiotec.2014.12.019

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title = "A novel in vitro permeability assay using three-dimensional cell culture system",

abstract = "Three-dimensional (3D) cell culture systems are well-known to better represent the in vivo environment and they are applied to many areas of research. Spheroid model is one of the systems of 3D cell culture and here in our research, a permeability assay utilizing the spheroids was developed. Number of cells forming the spheroids, initial compound concentration, and incubation time were optimized to provide the best assay performance. After development of the assay, it was evaluated with 22 commercially available compounds. The developed Caco-2 3D spheroid permeability assay demonstrated a reasonable correlation with human absorption values. The parallel artificial membrane permeability assay (PAMPA) was also performed for the same set of compounds and the results were compared with those of the 3D permeability assay. The correlation with human absorption values was shown to be improved with the 3D permeability assay. The successful development of the Caco-2 3D spheroid permeability assay also suggests the potential application of the 3D cell culture systems to other areas of pharmacokinetic research.",

author = "Lee, {Jong Bong} and Son, {Sung Hwa} and Park, {Min Chul} and Kim, {Tae Hwan} and Kim, {Min Gi} and Yoo, {Sun Dong} and Sunghoon Kim",

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AU - Lee, Jong Bong

AU - Son, Sung Hwa

AU - Park, Min Chul

AU - Kim, Tae Hwan

AU - Kim, Min Gi

AU - Yoo, Sun Dong

AU - Kim, Sunghoon

N1 - Funding Information: This work was supported by the Global Frontier Project (grants NRF-M3A6A4-2010-0029785 ) of National Research Foundation funded by the Ministry of Science, ICT & Future Planning (MSIP) of Korea. This work was also supported by a grant from Gyeonggi Research Development Program . Publisher Copyright: © 2015 Elsevier B.V.

PY - 2015/7/10

Y1 - 2015/7/10

N2 - Three-dimensional (3D) cell culture systems are well-known to better represent the in vivo environment and they are applied to many areas of research. Spheroid model is one of the systems of 3D cell culture and here in our research, a permeability assay utilizing the spheroids was developed. Number of cells forming the spheroids, initial compound concentration, and incubation time were optimized to provide the best assay performance. After development of the assay, it was evaluated with 22 commercially available compounds. The developed Caco-2 3D spheroid permeability assay demonstrated a reasonable correlation with human absorption values. The parallel artificial membrane permeability assay (PAMPA) was also performed for the same set of compounds and the results were compared with those of the 3D permeability assay. The correlation with human absorption values was shown to be improved with the 3D permeability assay. The successful development of the Caco-2 3D spheroid permeability assay also suggests the potential application of the 3D cell culture systems to other areas of pharmacokinetic research.

AB - Three-dimensional (3D) cell culture systems are well-known to better represent the in vivo environment and they are applied to many areas of research. Spheroid model is one of the systems of 3D cell culture and here in our research, a permeability assay utilizing the spheroids was developed. Number of cells forming the spheroids, initial compound concentration, and incubation time were optimized to provide the best assay performance. After development of the assay, it was evaluated with 22 commercially available compounds. The developed Caco-2 3D spheroid permeability assay demonstrated a reasonable correlation with human absorption values. The parallel artificial membrane permeability assay (PAMPA) was also performed for the same set of compounds and the results were compared with those of the 3D permeability assay. The correlation with human absorption values was shown to be improved with the 3D permeability assay. The successful development of the Caco-2 3D spheroid permeability assay also suggests the potential application of the 3D cell culture systems to other areas of pharmacokinetic research.

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A novel in vitro permeability assay using three-dimensional cell culture system

Abstract

Bibliographical note

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