Inhibition of influenza virus infection in mice by pulmonary administration of a spray dried antiviral drug.

Autor: Heida R; Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, 9713 AV Groningen, the Netherlands., Jacob Silva PH; Institute of Materials, Ecole Polytechnique Fédérale de Lausanne, Lausanne 1015 Switzerland., Akkerman R; Department of Medical Microbiology and Infection Prevention, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands., Moser J; Department of Critical Care, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the Netherlands; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the Netherlands., de Vries-Idema J; Department of Medical Microbiology and Infection Prevention, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands., Bornet A; Institute of Materials, Ecole Polytechnique Fédérale de Lausanne, Lausanne 1015 Switzerland., Pawar S; Institute of Materials, Ecole Polytechnique Fédérale de Lausanne, Lausanne 1015 Switzerland., Stellacci F; Institute of Materials, Ecole Polytechnique Fédérale de Lausanne, Lausanne 1015 Switzerland., Frijlink HW; Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, 9713 AV Groningen, the Netherlands., Huckriede ALW; Department of Medical Microbiology and Infection Prevention, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands., Hinrichs WLJ; Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, 9713 AV Groningen, the Netherlands. Electronic address: w.l.j.hinrichs@rug.nl.
Jazyk: angličtina
Zdroj: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V [Eur J Pharm Biopharm] 2024 Nov; Vol. 204, pp. 114507. Date of Electronic Publication: 2024 Sep 18.
DOI: 10.1016/j.ejpb.2024.114507
Abstrakt: Increasing resistance to antiviral drugs approved for the treatment of influenza urges the development of novel compounds. Ideally, this should be complemented by a careful consideration of the administration route. 6'siallyllactosamine-functionalized β-cyclodextrin (CD-6'SLN) is a novel entry inhibitor that acts as a mimic of the primary attachment receptor of influenza, sialic acid. In this study, we aimed to develop a dry powder formulation of CD-6'SLN to assess its in vivo antiviral activity after administration via the pulmonary route. By means of spray drying the compound together with trileucine, a dispersion enhancer, we created a powder that retained the antiviral effect of the drug, remained stable under elevated temperature conditions and performed well in a dry powder inhaler. To test the efficacy of the dry powder drug against influenza infection in vivo, infected mice were treated with CD-6'SLN using an aerosol generator that allowed for the controlled administration of powder formulations to the lungs of mice. CD-6'SLN was effective in mitigating the course of the disease compared to the control groups, reflected by lower disease activity scores and by the prevention of virus-induced IL-6 production. Our data show that CD-6'SLN can be formulated as a stable dry powder that is suitable for use in a dry powder inhaler and is effective when administered via the pulmonary route to influenza-infected mice.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Francesco Stellacci is inventor on patent number WO 2018/015465 A1 − Virucidal compounds and uses thereof. Francesco Stellacci and Paulo H. Jacob Silva are co-founders of Asterivir, a start-up company that focuses on developing novel antivirals. The employer of Henderik W. Frijlink holds a license agreement with PureIMS on the Twincer and Cyclops dry powder inhalers. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; nor in the writing of the manuscript or in the decision to submit the article for publication.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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