Abstract
Recently, various types of cultured cells have been used to research the mechanisms of transport and metabolism of drugs. Although many studies using cultured cell systems have been published, a comparison of different cultured cell systems has never been reported. In this study, Caco-2, Calu-3, Madin–Darby canine kidney (MDCK), EpiAirway and MucilAir were used as popular in vitro cell culture systems, and the permeability of model compounds across these cell systems was evaluated to compare barrier characteristics and to clarify their usefulness as an estimation system for nasal drug absorption in rats. MDCK unexpectedly showed the best correlation (r = 0.949) with the fractional absorption (Fn) in rats. Secondly, a high correlation was observed in Calu-3 (r = 0.898). Also, Caco-2 (r = 0.787) and MucilAir (r = 0.750) showed a relatively good correlation with Fn. The correlation between Fn and permeability to EpiAirway was the poorest (r = 0.550). Because EpiAirway forms leakier tight junctions than other cell culture systems, the paracellular permeability was likely overestimated with this system. On the other hand, because MDCK formed such tight cellular junctions that compounds of paracellular model were less likely permeated, the paracellular permeability could be underestimated. Calu-3, Caco-2 and MucilAir form suitable cellular junctions and barriers, indicating that those cell systems enable the precise estimation of nasal drug absorption.
Highlights
In vitro studies using cultured cells have been carried out to predict drug absorption and to clarify the influence of metabolic enzymes and transporters associated with in vivo membrane transport of drugs after oral [1,2], nasal [3,4], pulmonary [5], and dermal [6] administration
Some human respiratory and nasal epithelial cell culture systems, such as the EpiAirway and MucilAir systems, have been developed and used to estimate in vivo human nasal permeability. These systems are ready-to-use and feature three-dimensional mucociliary tissue models consisting of epithelial cells and goblet cells from the trachea/bronchus (EpiAirway) and the bronchus (MucilAir) of healthy humans. These commercial systems are available as co-culture systems, which can be used for the estimation of human nasal permeability, and toxicity [7] and virus infection [8], among others
Reagents and the media used for Caco-2, Madin–Darby canine kidney (MDCK), and Calu-3 cultures and the preparation of monolayers were purchased from Sigma-Aldrich (St Louis, MO, USA) and Gibco Laboratories (Lenexa, KS, USA), respectively
Summary
In vitro studies using cultured cells have been carried out to predict drug absorption and to clarify the influence of metabolic enzymes and transporters associated with in vivo membrane transport of drugs after oral [1,2], nasal [3,4], pulmonary [5], and dermal [6] administration. Some human respiratory and nasal epithelial cell culture systems, such as the EpiAirway and MucilAir systems, have been developed and used to estimate in vivo human nasal permeability These systems are ready-to-use and feature three-dimensional mucociliary tissue models consisting of epithelial cells and goblet cells from the trachea/bronchus (EpiAirway) and the bronchus (MucilAir) of healthy humans. These commercial systems are available as co-culture systems, which can be used for the estimation of human nasal permeability, and toxicity [7] and virus infection [8], among others. The manufacturer of EpiAirway indicates that the shelf life under storage at 4 ◦C, including the delivery time of tissues, may be up to 3 days, and that extended storage periods are not recommended unless necessary
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