Drug delivery characteristics of the progenitor bronchial epithelial cell line VA10

Berglind Eva Benediktsdóttir; Ari Jón Arason; Skarphédinn Halldórsson; Thórarinn Gudjónsson; Már Másson; Ólafur Baldursson

doi:10.1007/s11095-012-0919-x

Drug delivery characteristics of the progenitor bronchial epithelial cell line VA10

Berglind Eva Benediktsdóttir, Ari Jón Arason, Skarphédinn Halldórsson, Thórarinn Gudjónsson, Már Másson, Ólafur Baldursson^*

^*Corresponding author for this work

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

10 Citations (Scopus)

Abstract

Purpose: To determine the integrity and permeability properties of the immortalized human VA10 bronchial epithelial cell line for its suitability as an in vitro drug permeation model. Methods: Cells were grown under liquid-covered culture (LCC) or air-liquid interface (ALI) culture, characterized using electron microscopy and immunostaining. Integrity was measured using transepithelial electrical resistance (TER) and permeability of fluorescein sodium (Flu-Na). General permeability was established with dextrans and model drugs and P-glycoprotein (P-gp) function determined with bidirectional flux of rhodamine-123. Results: ALI culture resulted in 2-3 cell layers with differentiation towards ciliated cells but LCC showed undifferentiated morphology. VA10 cells formed TJ, with higher TER in LCC than ALI (∼2500 vs. ∼1200 Ω*cm²) and Flu-Na permeability ∼1-2 × 10^-7 cm/s. ALI cultured cells expressed P-gp and distinguished between compounds depending on lipophilicity and size, consistent with previous data from Calu-3 and 16HBE14o-cell lines. Conclusions: ALI cultured cell layers capture the in vivo-like phenotype of bronchial epithelium and form functional cell barrier capable of discriminating between compounds depending on physiochemical properties. The VA10 cell line is an important alternative to previously published cell lines and a relevant model to study airway drug delivery in vitro.

Original language	English
Pages (from-to)	781-791
Number of pages	11
Journal	Pharmaceutical Research
Volume	30
Issue number	3
DOIs	https://doi.org/10.1007/s11095-012-0919-x
Publication status	Published - Mar 2013

Bibliographical note

Funding Information:
Financial support from the Eimskip Fund of University of Iceland, the University of Iceland Research Fund, the Land-spitali University Hospital Science Fund and the Bergthóru and Thorsteins Scheving Thorsteinssonar Fund is gratefully acknowledged. We thank Professor Magnus Karl Magnusson for critical discussion and good advice, Sigrún Kristjánsdóttir at the Pathology Department of Landspitali University Hospital for her contribution to the paraffin prepared samples and Bergthóra S. Snorradóttir at the University of Iceland for help with the HPLC.

Other keywords

air-liquid interface culture
airway permeability
differentiation
drug delivery
human bronchial epithelial cells

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10.1007/s11095-012-0919-x

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title = "Drug delivery characteristics of the progenitor bronchial epithelial cell line VA10",

abstract = "Purpose: To determine the integrity and permeability properties of the immortalized human VA10 bronchial epithelial cell line for its suitability as an in vitro drug permeation model. Methods: Cells were grown under liquid-covered culture (LCC) or air-liquid interface (ALI) culture, characterized using electron microscopy and immunostaining. Integrity was measured using transepithelial electrical resistance (TER) and permeability of fluorescein sodium (Flu-Na). General permeability was established with dextrans and model drugs and P-glycoprotein (P-gp) function determined with bidirectional flux of rhodamine-123. Results: ALI culture resulted in 2-3 cell layers with differentiation towards ciliated cells but LCC showed undifferentiated morphology. VA10 cells formed TJ, with higher TER in LCC than ALI (∼2500 vs. ∼1200 Ω*cm2) and Flu-Na permeability ∼1-2 × 10-7 cm/s. ALI cultured cells expressed P-gp and distinguished between compounds depending on lipophilicity and size, consistent with previous data from Calu-3 and 16HBE14o-cell lines. Conclusions: ALI cultured cell layers capture the in vivo-like phenotype of bronchial epithelium and form functional cell barrier capable of discriminating between compounds depending on physiochemical properties. The VA10 cell line is an important alternative to previously published cell lines and a relevant model to study airway drug delivery in vitro.",

keywords = "air-liquid interface culture, airway permeability, differentiation, drug delivery, human bronchial epithelial cells",

author = "Benediktsd{\'o}ttir, {Berglind Eva} and Arason, {Ari J{\'o}n} and Skarph{\'e}dinn Halld{\'o}rsson and Th{\'o}rarinn Gudj{\'o}nsson and M{\'a}r M{\'a}sson and {\'O}lafur Baldursson",

note = "Funding Information: Financial support from the Eimskip Fund of University of Iceland, the University of Iceland Research Fund, the Land-spitali University Hospital Science Fund and the Bergth{\'o}ru and Thorsteins Scheving Thorsteinssonar Fund is gratefully acknowledged. We thank Professor Magnus Karl Magnusson for critical discussion and good advice, Sigr{\'u}n Kristj{\'a}nsd{\'o}ttir at the Pathology Department of Landspitali University Hospital for her contribution to the paraffin prepared samples and Bergth{\'o}ra S. Snorrad{\'o}ttir at the University of Iceland for help with the HPLC.",

year = "2013",

month = mar,

doi = "10.1007/s11095-012-0919-x",

language = "English",

volume = "30",

pages = "781--791",

journal = "Pharmaceutical Research",

issn = "0724-8741",

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T1 - Drug delivery characteristics of the progenitor bronchial epithelial cell line VA10

AU - Benediktsdóttir, Berglind Eva

AU - Arason, Ari Jón

AU - Halldórsson, Skarphédinn

AU - Gudjónsson, Thórarinn

AU - Másson, Már

AU - Baldursson, Ólafur

N1 - Funding Information: Financial support from the Eimskip Fund of University of Iceland, the University of Iceland Research Fund, the Land-spitali University Hospital Science Fund and the Bergthóru and Thorsteins Scheving Thorsteinssonar Fund is gratefully acknowledged. We thank Professor Magnus Karl Magnusson for critical discussion and good advice, Sigrún Kristjánsdóttir at the Pathology Department of Landspitali University Hospital for her contribution to the paraffin prepared samples and Bergthóra S. Snorradóttir at the University of Iceland for help with the HPLC.

PY - 2013/3

Y1 - 2013/3

N2 - Purpose: To determine the integrity and permeability properties of the immortalized human VA10 bronchial epithelial cell line for its suitability as an in vitro drug permeation model. Methods: Cells were grown under liquid-covered culture (LCC) or air-liquid interface (ALI) culture, characterized using electron microscopy and immunostaining. Integrity was measured using transepithelial electrical resistance (TER) and permeability of fluorescein sodium (Flu-Na). General permeability was established with dextrans and model drugs and P-glycoprotein (P-gp) function determined with bidirectional flux of rhodamine-123. Results: ALI culture resulted in 2-3 cell layers with differentiation towards ciliated cells but LCC showed undifferentiated morphology. VA10 cells formed TJ, with higher TER in LCC than ALI (∼2500 vs. ∼1200 Ω*cm2) and Flu-Na permeability ∼1-2 × 10-7 cm/s. ALI cultured cells expressed P-gp and distinguished between compounds depending on lipophilicity and size, consistent with previous data from Calu-3 and 16HBE14o-cell lines. Conclusions: ALI cultured cell layers capture the in vivo-like phenotype of bronchial epithelium and form functional cell barrier capable of discriminating between compounds depending on physiochemical properties. The VA10 cell line is an important alternative to previously published cell lines and a relevant model to study airway drug delivery in vitro.

AB - Purpose: To determine the integrity and permeability properties of the immortalized human VA10 bronchial epithelial cell line for its suitability as an in vitro drug permeation model. Methods: Cells were grown under liquid-covered culture (LCC) or air-liquid interface (ALI) culture, characterized using electron microscopy and immunostaining. Integrity was measured using transepithelial electrical resistance (TER) and permeability of fluorescein sodium (Flu-Na). General permeability was established with dextrans and model drugs and P-glycoprotein (P-gp) function determined with bidirectional flux of rhodamine-123. Results: ALI culture resulted in 2-3 cell layers with differentiation towards ciliated cells but LCC showed undifferentiated morphology. VA10 cells formed TJ, with higher TER in LCC than ALI (∼2500 vs. ∼1200 Ω*cm2) and Flu-Na permeability ∼1-2 × 10-7 cm/s. ALI cultured cells expressed P-gp and distinguished between compounds depending on lipophilicity and size, consistent with previous data from Calu-3 and 16HBE14o-cell lines. Conclusions: ALI cultured cell layers capture the in vivo-like phenotype of bronchial epithelium and form functional cell barrier capable of discriminating between compounds depending on physiochemical properties. The VA10 cell line is an important alternative to previously published cell lines and a relevant model to study airway drug delivery in vitro.

KW - air-liquid interface culture

KW - airway permeability

KW - differentiation

KW - drug delivery

KW - human bronchial epithelial cells

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DO - 10.1007/s11095-012-0919-x

M3 - Article

C2 - 23135824

AN - SCOPUS:84878870686

SN - 0724-8741

VL - 30

SP - 781

EP - 791

JO - Pharmaceutical Research

JF - Pharmaceutical Research

IS - 3

ER -

Drug delivery characteristics of the progenitor bronchial epithelial cell line VA10

Abstract

Bibliographical note

Other keywords

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