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.
Dimova
S
S
Laboratory for Pharmacotechnology and Biopharmacy, Katholieke Universiteit Leuven, Herestraat 49, O&N Gasthuisberg, Leuven 3000, Belgium.
Mugabowindekwe
R
R
Willems
T
T
Brewster
M E
ME
Noppe
M
M
Ludwig
A
A
Jorissen
M
M
Augustijns
P
P
D000281:Administration, Intranasal; D000704:Analysis of Variance; D000998:Antiviral Agents / Q000009:adverse effects* / Q000737:chemistry / Q000494:pharmacology; D002478:Cells, Cultured; D002923:Cilia / Q000187:drug effects / Q000502:physiology / Q000821:virology; D006801:Humans; D009297:Nasal Mucosa / Q000187:drug effects* / Q000502:physiology / Q000821:virology*; D011794:Quercetin / Q000009:adverse effects* / Q000031:analogs & derivatives / Q000494:pharmacology; D012229:Rhinovirus / Q000187:drug effects / Q000502:physiology
D000998:Antiviral Agents; D011794:Quercetin