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, character...
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Published in | Pharmaceutical research Vol. 30; no. 3; pp. 781 - 791 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Boston
Springer US
01.03.2013
Springer Springer Nature B.V |
Subjects | |
Online Access | Get full text |
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Summary: | 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*cm
2
) 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
. |
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ISSN: | 0724-8741 1573-904X |
DOI: | 10.1007/s11095-012-0919-x |