Pulmonary delivery of favipiravir inhalation solution for COVID-19 treatment: in vitro characterization, stability, in vitro cytotoxicity, and antiviral activity using real time cell analysis

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dc.authoridAybige Ertürk / 0000-0002-5179-5865en_US
dc.authorscopusidAybige Ertürk / 57312790100
dc.authorwosidAybige Ertürk / GAQ-1057-2022en_US
dc.date.accessioned2022-09-19T12:05:36Z
dc.date.available2022-09-19T12:05:36Z
dc.date.issued2022en_US
dc.departmentİstinye Üniversitesi, Eczacılık Fakültesi, Eczacılık Teknolojisi Bölümüen_US
dc.description.abstractFavipiravir, an RNA-dependent RNA polymerase (RdRp) inhibitor, is used to treat patients infected with influenza virus and most recently with SARS-CoV-2. However, poor accumulation of favipiravir in lung tissue following oral administration has required an alternative method of administration that directly targets the lungs. In this study, an inhalation solution of favipiravir at a concentration of 2 mg mL(-1) was developed and characterized for the first time. The chemical stability of inhaled favipiravir solution in two different media, phosphate buffer saline (PBS) and normal saline (NS), was investigated under different conditions: 5 +/- 3 degrees C, 25 +/- 2 degrees C/60% RH +/- 5% RH, and 40 +/- 2 degrees C/75% RH +/- 5% RH; in addition to constant light exposure. As a result, favipiravir solution in PBS revealed superior stability over 12 months at 5 +/- 3 degrees C. Antiviral activity of favipiravir was assessed at the concentrations between 0.25 and 3 mg mL(-1) with real time cell analyzer on Vero-E6 that were infected with SARS-CoV-2/B.1.36. The optimum concentration was found to be 2 mg mL(-1), where minimum toxicity and sufficient antiviral activity was observed. Furthermore, cell viability assay against Calu-3 lung epithelial cells confirmed the biocompatibility of favipiravir at concentrations up to 50 mu M (7.855 mg mL(-1)). The in vitro aerodynamic profiles of the developed inhaled favipiravir formulation, when delivered with soft-mist inhaler indicated good lung targeting properties. These results suggest that favipiravir solution prepared with PBS could be considered as a suitable and promising inhalation formulation for pulmonary delivery in the treatment of patients with COVID-19.en_US
dc.identifier.citationYildiz Pekoz, A., Akbal Dagistan, O., Fael, H., Culha, M., Erturk, A. (2022). Pulmonary delivery of favipiravir inhalation solution for COVID-19 treatment: in vitro characterization, stability, in vitro cytotoxicity, and antiviral activity using real time cell analysis. Drug Delivery, 29(1), 2846-2854.en_US
dc.identifier.doi10.1080/10717544.2022.2118398en_US
dc.identifier.endpage2854en_US
dc.identifier.issn1071-7544en_US
dc.identifier.issue1en_US
dc.identifier.scopus2-s2.0-85137233155en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage2846en_US
dc.identifier.urihttps://doi.org/10.1080/10717544.2022.2118398
dc.identifier.urihttps://hdl.handle.net/20.500.12713/3158
dc.identifier.volume29en_US
dc.identifier.wosWOS:000849959000001en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.institutionauthorErtürk, Aybige
dc.language.isoenen_US
dc.publisherTAYLOR & FRANCISen_US
dc.relation.ispartofDRUG DELIVERYen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectFavipiraviren_US
dc.subjectCOVID-19en_US
dc.subjectAntiviral Activityen_US
dc.subjectInhaled Formulationen_US
dc.subjectRespiratoryen_US
dc.titlePulmonary delivery of favipiravir inhalation solution for COVID-19 treatment: in vitro characterization, stability, in vitro cytotoxicity, and antiviral activity using real time cell analysisen_US
dc.typeArticleen_US

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