20.500.12556/RUL-136220 In vitro ciliotoxicity and cytotoxicity testing of repeated chronic exposure to topical nasal formulations for safety studies Certain active drugs and excipients of nasal formulations may impair ciliary function and mucociliary clearance. The ciliary beat frequency (CBF) is a key parameter for determining mucociliary clearance rate, and in vitro assessments of CBF have proven to be accurate and reproducible. Since topical nasal formulations are applied with repeated doses, it is essential to elucidate their chronic, as opposed to acute, effect on mucociliary clearance and nasal mucosa. The aim of this study was to assess for the first time the ciliotoxicity and cytotoxicity of nasal sprays intended for chronic treatment (with repeated doses) using a previously designed set-up for CBF measurements. For 2 weeks, the 3D nasal MucilAir™ in vitro models were treated daily with undiluted or clinically relevant doses of mometasone nasal spray, placebo nasal spray, culture medium, or they were untreated. We demonstrated a dose-dependent and time-dependent (cumulative) effect of the nasal sprays on ciliary activity and cytotoxicity using CBF measurements and ultrastructural analysis, respectively. Our results indicate that repeated administration of clinically relevant doses of mometasone nasal spray is safe for in vivo use, which is in good agreement with a previous clinical study. Overall, our study suggests that such in vitro assays have great potential for topical nasal drug screening. nasal drug formulations mucociliary clearance cytotoxicity ciliary beat frequency nasal in vitro model repeated exposure ciliotoxicity ultrastructural analysis drug safety formulacije zdravil za nos mukociliarni očistek citotoksičnost true false true Angleški jezik Slovenski jezik Članek v reviji 2022-04-20 11:35:41 2022-04-20 11:35:45 2022-09-15 04:13:35 0000-00-00 00:00:00 2021 0 0 18 str. iss. 11, art. 1750 Vol. 13 2021 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 615.2 1999-4923 10.3390/pharmaceutics13111750 81714179 pharmaceutics-13-01750-v3.pdf pharmaceutics-13-01750-v3.pdf 1 DD1A032F1D013D4EB417F6FCF21DCA1C e142ec8914f9521ae1c8ce8a9bab8b1965667a9ae07fcbedbf9ebaa5ee7775e4 b97a9c60-c08d-11ec-8aca-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=155750 https://www.mdpi.com/1999-4923/13/11/1750 0 8b470a4e-c08d-11ec-8aca-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=155749 Medicinska fakulteta Fakulteta za farmacijo 0 0 0