Fluticasone uptake across Calu-3 cells is mediated by salmeterol when deposited as a combination powder inhaler
- Publication Type:
- Journal Article
- Respirology, 2013, 18 (8), pp. 1197 - 1201
- Issue Date:
Background and objective We assessed whether co-deposition of a long-acting β2-agonist and a corticosteroid affects their respective transport rates across epithelial cells. Methods Drug particles were deposited on the air-interface culture of Calu-3 cells using a twin-stage impinger. We compared the transport rate of salmeterol and fluticasone across the epithelial cells using commercially available formulations (Serevent, Flixotide and Seretide). The transepithelial resistance of Calu-3 cells was measured before and after each deposition to monitor epithelial resistance. Results The codeposition of salmeterol and fluticasone had no significant effect on transport of salmeterol through the cell layer. In contrast, the rate of fluticasone propionate transport in presence of salmeterol xinofoate was significantly lower (0.53 ± 0.20%) compared with the single fluticasone formulation (2.36 ± 0.97%). Furthermore, the resistance of the epithelial cells was significantly increased after salmeterol deposition from both single and combination products. Conclusions Our data demonstrate that salmeterol may decrease the permeability of epithelial cells, resulting in slower fluticasone transport across Calu-3 epithelial monolayers. The subsequent increased residence time of fluticasone in the airways could prolong its anti-inflammatory effects. This study shows for the first time that salmeterol prolongs the transport of fluticasone across the epithelial cell layer following codeposition of salmeterol and fluticasone particles on epithelial cell cultures. This may increase residence time of fluticasone in the airways and result in prolonged anti-inflammatory effects of this corticosteroid. See Editorial, page 1165 © 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.
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