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...

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Autores principales:	Larisa Tratnjek, Nadica Sibinovska, Katja Kristan, Mateja Erdani Kreft
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	nasal drug formulations mucociliary clearance ciliary beat frequency nasal in vitro model repeated exposure ciliotoxicity Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/775667f3be4745bda76638b29ea4b91d
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spelling	oai:doaj.org-article:775667f3be4745bda76638b29ea4b91d2021-11-25T18:40:22ZIn Vitro Ciliotoxicity and Cytotoxicity Testing of Repeated Chronic Exposure to Topical Nasal Formulations for Safety Studies10.3390/pharmaceutics131117501999-4923https://doaj.org/article/775667f3be4745bda76638b29ea4b91d2021-10-01T00:00:00Zhttps://www.mdpi.com/1999-4923/13/11/1750https://doaj.org/toc/1999-4923Certain 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.Larisa TratnjekNadica SibinovskaKatja KristanMateja Erdani KreftMDPI AGarticlenasal drug formulationsmucociliary clearanceciliary beat frequencynasal in vitro modelrepeated exposureciliotoxicityPharmacy and materia medicaRS1-441ENPharmaceutics, Vol 13, Iss 1750, p 1750 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	nasal drug formulations mucociliary clearance ciliary beat frequency nasal in vitro model repeated exposure ciliotoxicity Pharmacy and materia medica RS1-441
spellingShingle	nasal drug formulations mucociliary clearance ciliary beat frequency nasal in vitro model repeated exposure ciliotoxicity Pharmacy and materia medica RS1-441 Larisa Tratnjek Nadica Sibinovska Katja Kristan Mateja Erdani Kreft In Vitro Ciliotoxicity and Cytotoxicity Testing of Repeated Chronic Exposure to Topical Nasal Formulations for Safety Studies
description	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.
format	article
author	Larisa Tratnjek Nadica Sibinovska Katja Kristan Mateja Erdani Kreft
author_facet	Larisa Tratnjek Nadica Sibinovska Katja Kristan Mateja Erdani Kreft
author_sort	Larisa Tratnjek
title	In Vitro Ciliotoxicity and Cytotoxicity Testing of Repeated Chronic Exposure to Topical Nasal Formulations for Safety Studies
title_short	In Vitro Ciliotoxicity and Cytotoxicity Testing of Repeated Chronic Exposure to Topical Nasal Formulations for Safety Studies
title_full	In Vitro Ciliotoxicity and Cytotoxicity Testing of Repeated Chronic Exposure to Topical Nasal Formulations for Safety Studies
title_fullStr	In Vitro Ciliotoxicity and Cytotoxicity Testing of Repeated Chronic Exposure to Topical Nasal Formulations for Safety Studies
title_full_unstemmed	In Vitro Ciliotoxicity and Cytotoxicity Testing of Repeated Chronic Exposure to Topical Nasal Formulations for Safety Studies
title_sort	in vitro ciliotoxicity and cytotoxicity testing of repeated chronic exposure to topical nasal formulations for safety studies
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/775667f3be4745bda76638b29ea4b91d
work_keys_str_mv	AT larisatratnjek invitrociliotoxicityandcytotoxicitytestingofrepeatedchronicexposuretotopicalnasalformulationsforsafetystudies AT nadicasibinovska invitrociliotoxicityandcytotoxicitytestingofrepeatedchronicexposuretotopicalnasalformulationsforsafetystudies AT katjakristan invitrociliotoxicityandcytotoxicitytestingofrepeatedchronicexposuretotopicalnasalformulationsforsafetystudies AT matejaerdanikreft invitrociliotoxicityandcytotoxicitytestingofrepeatedchronicexposuretotopicalnasalformulationsforsafetystudies
_version_	1718410842569965568

In Vitro Ciliotoxicity and Cytotoxicity Testing of Repeated Chronic Exposure to Topical Nasal Formulations for Safety Studies

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