Drug Delivery Characteristics of the Progenitor Bronchial Epithelial Cell Line VA10

• Published in: Pharmaceutical research Vol. 30; no. 3; pp. 781 - 791
• Main Authors: Benediktsdóttir, Berglind Eva, Arason, Ari Jón, Halldórsson, Skarphédinn, Gudjónsson, Thórarinn, Másson, Már, Baldursson, Ólafur
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.03.2013; Springer; Springer Nature B.V
• Subjects: Alcohols - pharmacokinetics; ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism; Biochemistry; Biological and medical sciences; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Bronchi - cytology; Cell Line; Cellular biology; Dextrans - pharmacokinetics; Drug delivery systems; Epithelial Cells - cytology; Epithelial Cells - metabolism; General pharmacology; Humans; Medical Law; Medical sciences; Permeability; Pharmaceutical technology. Pharmaceutical industry; Pharmacology; Pharmacology. Drug treatments; Pharmacology/Toxicology; Pharmacy; Research Paper; Stem Cells - metabolism; air-liquid interface culture; airway permeability; differentiation; drug delivery; human bronchial epithelial cells; Human; Pharmaceutical technology; Stem cell; Drug carrier; Permeability; In vitro; Respiratory tract; Established cell line; Epithelial cell; Progenitor cell
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-012-0919-x

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 .