Transport of anti-allergic drugs across the passage cultured human nasal epithelial cell monolayer

Abstract

The purpose of this study was to investigate the nasal absorption characteristics of a series of anti-allergic drugs across the human nasal epithelial cell monolayer, which was passage cultured by the liquid-covered culture (LCC) method on Transwell ®. Characterization of this cell culture model was achieved by bioelectric measurements and morphological studies. The passages 2–4 of cell monolayers exhibited the TEER value of 1731 ± 635 Ω cm 2 after 2 days of seeding and maintained high TEER value for 4–6 days. Morphological study by TEM and SEM showed the existence of the tight junctions, and the cuboidal shaped epithelial cells monolayer. A series of anti-allergic drugs, albuterol hemisulfate, albuterol, fexofenadine HCl, dexamethasone, triamcinolon acetonide, and budesonide were selected as model compounds for transport studies. All the drugs were assayed using reversed-phase HPLC under isocratic conditions. Results indicated that within the log P (apparent 1-octanol/water partition coefficient) range from −1.58 (albuterol) to 3.21 (budesonide), there existed 100-fold difference in the apparent permeability coefficients ( P app). A log-linear relationship was shown between the drug log P and the P app across passaged human nasal epithelial monolayers. The amount of fexofenadine HCl and dexamethasone across passaged human nasal cell monolayers was concentration-dependent in the direction of apical to basolateral. The direction dependent transport studies were investigated among all these drugs and no significant difference in the two directions was observed. In conclusion, this LCC passaged human nasal epithelial culture model may be a useful in vitro model for studying the passive transport processes in nasal drug delivery.