PI-058 - ASSESSMENT OF INHALED CORTICOSTEROIDS PERMEABILITY IN DIFFERENT IN VITRO MODELS TO PREDICT PULMONARY DRUG ABSORPTION

B. Eltanameli¹, J. Pineiro Llanes¹, Y. Zang¹, Y. Zhang², Y. Lang¹, J. Bulitta¹, R. Cristofoletti³; ¹University of Florida, Orlando, FL, USA, ²University of Florida, Orlando, FL, University of Florida, ³University of Florida, Orlando,FL, USA.

Background: Pulmonary absorption of orally inhaled drug products is critical to their efficacy, particularly for treating local lung conditions like asthma. Drug permeability is essential in determining pulmonary absorption, distribution, and efficacy of inhaled pharmaceuticals. We aim to assess the permeability of fluticasone and budesonide in vitro across bronchial and alveolar cell lines. We also aim to evaluate the effect of the mucus layer and cilia beating on drug permeability by using MucilAir™, which is a bioengineered bronchial epithelium tissue derived from primary cells from healthy donors.

Methods: Calu-3, from bronchial origin, and NCI-H441, from alveolar origin, were seeded on Transwells® for 10-14 days to form polarized cell monolayer and were monitored by measuring the transepithelial electrical resistance (TEER). MucilAir™, represent a fully differentiated respiratory epithelium that was maintained per the manufacturer’s instructions. Apical-to-basolateral permeability for the inhaled corticosteroids were measured in the three in vitro systems. Metoprolol and atenolol were included as high and low permeability standards, respectively. The in vitro permeability results were compared to the ex vivo effective permeability (Peff) of the isolated perfused lung available in the literature.

Results: Calu-3 and NCI-H441 reached TEER of > 400 Ω·cm² and > 250 Ω·cm² respectively, indicating barrier integrity and mimicking human epithelial barriers essential for permeability studies. MucilAir™ exhibited a TEER value of 315 Ω·cm². Both fluticasone and budesonide showed high permeability results comparable to metoprolol in all investigated in vitro models. The coefficient of determination (R²) for Papp to Peff for the tested drugs was highest in MucilAir™, followed by Calu-3 and NCI-H441.

Conclusion: Calu-3, NCI-H441, and MucilAir™ form tight junctions, suggesting their suitability for estimating inhaled drug permeability. Fluticasone and budesonide exhibited high permeability, indicating rapid absorption across the lung epithelium. Permeability results imply that the mucus layer in the MucilAir™ model did not significantly affect the permeability of the tested corticosteroids, however, MucilAir™ better predicted the ex vivo corticosteroid permeability compared to the other models.