Mediated fluticasone uptake across calu-3 cells by salmeterol from a combination powder inhaler

Background and objective: We aimed to assess whether co-deposition of a long-acting β2-agonist and a steroid 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 from commercially available formulations (Serevent®, Flixotide® and Seretide®) across the epithelial cells. The transepithelial resistance of Calu-3 cells was measured before and after each deposition to monitor epithelial resistance.

Results: The co-deposition of salmeterol and fluticasone had no significant effect on transport of salmeterol through the cell layer, suggesting that salmeterol particles are deposited evenly across the cell line and each particle could have its own dissolution and uptake profile. In contrast, the rate of FP transport in presence of S was significantly lower (0.53 ± 0.20%) compared to the single FP formulation (2.36 ± 0.97%). Furthermore, the resistance of the epithelial cells was significantly increased after salmeterol deposition from both single and combination product.

Conclusions: Our data demonstrates that salmeterol may decrease the permeability of epithetical cells, resulting in slower fluticasone transport across Calu-3 epithelial monolayer. The subsequent increased residence time of fluticasone in the airways could prolong it’s anti-inflammatory effects.