An improved primary human nasal cell culture for the simultaneous determination of transepithelial transport and ciliary beat frequency

Abstract

Abstract Objectives 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 μm). Transepithelial transport and ciliary beat frequency values were measured every 15 min for 1 h. Key findings The apparent permeability coefficients (Papp) for atenolol (mainly paracellular transport) and propranolol (transcellular transport) amounted to 0.1 ± 0.1 and 23.7 ± 0.6 × 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 × 10−6 cm/s for absorptive and secretory transport, respectively) and was not affected by verapamil (10 μm), 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.