The aim of this work was to compare three existing mucus-secreting airway cell lines for use as models of the airways to study drug transport in the presence of mucus. Each cell line secreted mature, glycosylated mucins, evidenced by the enzyme-linked lectin assay. The secretagogue, adenylyl-imidodiphosphate, increased mucin secretion in SPOC1 (3.5-fold) and UNCN3T (1.5-fold) cells but not in Calu-3 cells. In a novel mucus-depleted (MD) model the amount of mucus in the non-depleted wells was 3-, 8- and 4-fold higher than in the mucus-depleted wells of the Calu-3, SPOC1 and UNCN3T cells respectively. The permeability of 'high mucus’ cells to testosterone was significantly less in SPOC1 and UNCN3T cells (P < 0.05) but not Calu-3 cells. Mucin secretion and cytokine release were investigated as indicators of drug irritancy in the SPOC1 and UNCN3T cell lines. A number of inhaled drugs significantly increased mucin secretion at high concentrations and the release of IL-6 and IL-8 from SPOC1 or UNCN3T cells (P < 0.05). SPOC1 and UNCN3T cell lines are better able to model the effect of mucus on drug absorption than the Calu-3 cell line and are proposed for use in assessing drug-mucus interactions in inhaled drug and formulation development.
|Number of pages||16|
|Journal||European Journal of Pharmaceutics and Biopharmaceutics|
|Publication status||Published - 29 Jul 2021|
Bibliographical noteFunding Information: The authors would like to acknowledge the kind gifts of the SPOC1 and UNCN3T cells from Cystic Fibrosis/Pulmonary Research and Treatment Centre, University of North Carolina, NC, US and the technical support of Dr Rosa Busquets with the LCMS and Dr Andy Overall with the qRT-PCR. This work was supported by BBSRC CASE (GSK) award [BB/J500331/1]. Funding Information: This work was supported by BBSRC CASE (GSK) award [BB/J500331/1].
- Airway epithelial cells
- Cell-based assay
- Drug absorption
- Mucus barrier
- Nasal drug delivery
- Permeability barrier
- Pulmonary drug delivery