An improved primary human nasal cell culture for the simultaneous determination of transepithelial transport and ciliary beat frequency.
OBJECTIVE
The aim was to establish a preclinical in-vitro system of the nasal mucosa for the simultaneous evaluation of nasal absorption and effects on ciliary activity.


METHODS
Human nasal epithelial cells were grown in collagen-coated transport inserts with transparent polyethylene terephthalate membranes (3 mum). Transepithelial transport and ciliary beat frequency values were measured every 15 min for 1 h.


RESULTS
The apparent permeability coefficients (P(app)) for atenolol (mainly paracellular transport) and propranolol (transcellular transport) amounted to 0.1 +/- 0.1 and 23.7 +/- 0.6 x 10(-6) cm/s, respectively, illustrating that the system can be used to discriminate between high permeability and low permeability compounds. Transport of talinolol (substrate for the P-glycoprotein efflux carrier) did not reveal polarity (0.3 +/- 0.2 and 0.2 +/- 0.1 x 10(-6) cm/s for absorptive and secretory transport, respectively) and was not affected by verapamil (10 muM), suggesting the absence of P-glycoprotein in the nasal cell culture. No significant effects of atenolol, propranolol and talinolol on ciliary beat frequency were observed (98 +/- 20% of the control condition after 60 min). Chlorocresol significantly decreased the ciliary activity but this decrease was not accompanied by effects on the transepithelial transport of atenolol, propranolol and talinolol.


CONCLUSIONS
A new system was developed which offers possibilities as a fast screening tool for studying the potential of compounds for nasal drug administration, since permeability and a possible cilio-toxic effect can be assessed simultaneously.
Mallants
Roel
R
Laboratory for Pharmacotechnology and Biopharmacy, Katholieke Universiteit Leuven, Belgium.
Vlaeminck
Valerie
V
Jorissen
Mark
M
Augustijns
Patrick
P
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000281:Administration, Intranasal; D000959:Antihypertensive Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001262:Atenolol / Q000493:pharmacokinetics / Q000494:pharmacology; D001692:Biological Transport; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D002923:Cilia / Q000187:drug effects / Q000502:physiology; D003408:Cresols / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D009079:Mucociliary Clearance; D009297:Nasal Mucosa / Q000166:cytology* / Q000378:metabolism*; D011412:Propanolamines / Q000493:pharmacokinetics / Q000494:pharmacology; D011433:Propranolol / Q000493:pharmacokinetics / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000959:Antihypertensive Agents; D003408:Cresols; D011412:Propanolamines; C006984:chlorocresol; C011550:talinolol; D001262:Atenolol; D011433:Propranolol