Enhancing effect of surfactants on fexofenadine.HCl transport across the human nasal epithelial cell monolayer.
The effect of various surfactants (sodium cholate, sodium taurocholate, Tween 80 and Poloxamer F68) on enhancing the transepithelial permeability of fexofenadine.HCl was evaluated in a human nasal epithelial cell monolayer model. The cytotoxicity of the surfactants on the human nasal epithelial cells was evaluated by the MTT assay. A dose-dependent reduction of cell viability was observed at higher than critical micelle concentration (CMC) of the surfactants, and the IC50 of non-ionic surfactants (Tween 80 and Poloxamer F68) was higher than that of ionic surfactants (sodium cholate and sodium taurocholate). The TEER values significantly decreased after 2 h incubation with the ionic surfactants, but were recovered after 24 h in the fresh culture media. Ionic surfactants significantly increased the transepithelial permeability (P(app)) of fexofenadine.HCl compared to the non-ionic surfactants. The reduction of TEER values upon exposing the cell monolayer to the surfactants for 2 h correlated well with the P(app) of fexofenadine.HCl, which suggests that the permeation-enhancing mechanism of the ionic surfactants is by altering the tight junction property of the paracellular pathway. F-actin staining showed that the effect of ionic surfactants on the tight junction is temporary and reversible, which is consistent with the TEER value recovery within 24 h. These results imply that ionic surfactants are potentially useful permeation enhancers for nasal delivery of hydrophilic compounds, such as fexofenadine.HCl. This study also indicated the usefulness of the human nasal epithelial cell monolayer model not only for evaluating the in vitro nasal drug transport but also for studying the mechanism and toxicity of enhancers.
Lin
Hongxia
H
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, South Korea.
Gebhardt
Matthias
M
Bian
Shengjie
S
Kwon
Kyoung Ae
KA
Shim
Chang-Koo
CK
Chung
Suk-Jae
SJ
Kim
Dae-Duk
DD
D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004357:Drug Synergism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005562:Formazans; D039563:Histamine H1 Antagonists, Non-Sedating / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D018613:Microscopy, Confocal; D009297:Nasal Mucosa / Q000187:drug effects* / Q000378:metabolism*; D020442:Poloxamer / Q000494:pharmacology; D011136:Polysorbates; D020358:Sodium Cholate / Q000494:pharmacology; D013501:Surface-Active Agents / Q000494:pharmacology*; D013656:Taurocholic Acid / Q000494:pharmacology; D016593:Terfenadine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D013778:Tetrazolium Salts
D005562:Formazans; D039563:Histamine H1 Antagonists, Non-Sedating; D011136:Polysorbates; D013501:Surface-Active Agents; D013778:Tetrazolium Salts; D020442:Poloxamer; C079782:MTT formazan; D013656:Taurocholic Acid; D016593:Terfenadine; C093230:fexofenadine; D020358:Sodium Cholate