Characterisation of Primary Air-Liquid Interface Culture of Nasal Epithelium for Nasal Drug Delivery

Authors: , , , , , , , ,

Background: The nasal route has been seen as a promising alternative to oral and parenteral routes for various therapeutics due to its non-invasive nature, rapid absorption, and circumvention of first pass metabolism. Hence, an in vitro model using human primary nasal epithelial cells could be the key to understanding important functions and parameters of the respiratory epithelium. The purpose of this study was to establish and characterise human nasal epithelium model to be used as a tool for the study of drug transport and simultaneously quantify drug effects on ciliary activity.
Methods: Nasal epithelial cells were obtained from human volunteers through nasal brushing. The cells were seeded onto cell culture inserts and cultured at the air-liquid interface for several weeks to allow for cell differentiation. Functional characteristics of epithelium, including tight junction formation and ciliary activity, were characterised using fluorescein sodium (flu-Na) permeability studies, transepithelial electrical resistance measurements and high-speed video microscopy, respectively.
Results: The epithelial cell monolayer displayed and maintained high TEER values of 811.8 ± 131.75 Ω cm2 up to 7 weeks in culture. The permeability of flu-Na started to plateau and ciliation >20% of the nasal epithelial monolayer was observed after 5 weeks in culture. The ciliary activity was found to have a mean beat frequency of 10.7± 1.6 Hz (healthy normal range 8.8 -14.09 Hz).
Conclusions: This study has established a primary nasal epithelium model that differentiates into a heterogeneous population of cells, produces functional cilia and viable tight junctions at the air-interface that could be used to address fundamental research questions relating to nasally delivered formulation.