TY - JOUR
T1 - A 'soft spot' for drug transport
T2 - modulation of cell stiffness using fatty acids and its impact on drug transport in lung model
AU - Haghi, Mehra
AU - Traini, Daniela
AU - Wood, Lisa G.
AU - Oliver, Brian
AU - Young, Paul M.
AU - Chrzanowski, Wojciech
PY - 2015
Y1 - 2015
N2 - The impact of a polyunsaturated fatty acid, arachidonic acid (AA), on membrane fluidity of epithelial cells and subsequent modulation of the drug transport was investigated. Membrane fluidity was assessed using molecular force microscopy. Calu-3 human bronchial epithelial cells were cultured on Transwell® inserts and the cell stiffness was assessed in the absence of fatty acids or in the presence of 30 μM AA. The morphology of the epithelial cells was distinctly different when AA was present, with the cell monolayer becoming more uniform. Furthermore the cell stiffness and variation in stiffness was lower in the presence of AA. In the fat-free medium, the median cell stiffness was 9.1 kPa which dropped to 2.1 kPa following exposure to AA. To further study this, transport of a common β2-agonist, salbutamol sulphate (SS) was measured in the presence of AA and in a fat free medium. The transport of SS was significantly higher when AA was present (0.61 ± 0.09 μg versus 0.11 ± 0.003 μg with and without AA respectively). It was evidenced that AA play a vital role in cell membrane fluidity and drug transport. This finding highlights the significance of the dietary fatty acids in transport and consequentially effectiveness of medications used to treat pulmonary diseases such as asthma.
AB - The impact of a polyunsaturated fatty acid, arachidonic acid (AA), on membrane fluidity of epithelial cells and subsequent modulation of the drug transport was investigated. Membrane fluidity was assessed using molecular force microscopy. Calu-3 human bronchial epithelial cells were cultured on Transwell® inserts and the cell stiffness was assessed in the absence of fatty acids or in the presence of 30 μM AA. The morphology of the epithelial cells was distinctly different when AA was present, with the cell monolayer becoming more uniform. Furthermore the cell stiffness and variation in stiffness was lower in the presence of AA. In the fat-free medium, the median cell stiffness was 9.1 kPa which dropped to 2.1 kPa following exposure to AA. To further study this, transport of a common β2-agonist, salbutamol sulphate (SS) was measured in the presence of AA and in a fat free medium. The transport of SS was significantly higher when AA was present (0.61 ± 0.09 μg versus 0.11 ± 0.003 μg with and without AA respectively). It was evidenced that AA play a vital role in cell membrane fluidity and drug transport. This finding highlights the significance of the dietary fatty acids in transport and consequentially effectiveness of medications used to treat pulmonary diseases such as asthma.
UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84925263956&partnerID=MN8TOARS
U2 - 10.1039/C4TB01928H
DO - 10.1039/C4TB01928H
M3 - Article
C2 - 32262905
SN - 2050-7518
VL - 3
SP - 2583
EP - 2589
JO - Journal of Materials Chemistry B
JF - Journal of Materials Chemistry B
IS - 13
ER -