Safety-assessment of 3-methoxyquercetin as an antirhinoviral compound for nasal application: effect on ciliary beat frequency.

It has been shown that 5,7,3',4'-tetrahydroxy-3-O-methylflavone (3-MQ) exhibits antipicornaviral activity. In order to explore the potential of 3-MQ as an antirhinoviral compound for nasal application, the effect of 3-MQ on the ciliary beat frequency (CBF) of human nasal epithelial cells was studied in vitro in the absence or presence of solubility/absorption enhancers (hydroxypropyl-beta-cyclodextrin (HP-beta-CD) or polysorbate 80). Nasal epithelial cells were obtained by protease digestion of surgical specimens of human nasal polyps, and used at confluency. The effect of 3-MQ (2, 10, and 20 microg/ml), HP-beta-CD (1, 3, and 10% (w/v)), polysorbate 80 (0.1, 0.3, and 1% (w/v)), and of the combination of 3-MQ with 3% HP-beta-CD or 1% polysorbate 80, on the CBF was determined by computerized microscope photometry 15 min after incubation with the test compounds; recovery was determined 35 min after rinsing. HP-beta-CD at 1 and 3% did not affect CBF; a reversible decrease (by 37%) was observed at 10%. Polysorbate 80 caused a reversible cilio-inhibitory effect of 40, 53, and 49% at 0.1, 0.3, and 1%, respectively. At 2 and 10 microg/ml, 3-MQ showed a reversible cilio-stimulatory effect of 18 and 14%, respectively. Combined with 3% HP-beta-CD, the reversible cilio-stimulatory effect of 2 microg/ml 3-MQ was preserved, while 10 and 20 microg/ml 3-MQ did not affect the CBF. The combination of polysorbate 80 (1%) and 3-MQ decreased the CBF, which could be attributed to the presence of polysorbate 80. In conclusion, no ciliotoxic effect could be observed for 3-MQ (up to 20 microg/ml) in the absence or presence of HP-beta-CD (3%). The potential of this combination as an antirhinoviral formulation for nasal application will be further explored.