In vitro ciliotoxicity and cytotoxicity testing of repeated chronic exposure to topical nasal formulations for safety studies

Tratnjek, Larisa (author), Sibinovska, Nadica (author), Kristan, Katja (author), Erdani-Kreft, Mateja (author)

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.

• Language: English
• Keywords: nasal drug formulations, mucociliary clearance, cytotoxicity, ciliary beat frequency, nasal in vitro model, repeated exposure, ciliotoxicity, ultrastructural analysis, drug safety
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine; FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2021
• Number of pages: 18 str.
• Numbering: Vol. 13, iss. 11, art. 1750
• PID: 20.500.12556/RUL-136220
• UDC: 615.2
• ISSN on article: 1999-4923
• DOI: 10.3390/pharmaceutics13111750
• COBISS.SI-ID: 81714179
• Publication date in RUL: 20.04.2022

Record is a part of a journal

• Title: Pharmaceutics
• Shortened title: Pharmaceutics
• Publisher: MDPI
• ISSN: 1999-4923
• COBISS.SI-ID: 517949977

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 01.11.2021

Secondary language

• Language: Slovenian
• Keywords: formulacije zdravil za nos, mukociliarni očistek, citotoksičnost