Rick Heida , Paulo H. Jacob Silva , Renate Akkerman , Jill Moser , Jacqueline de Vries-Idema , Aurélien Bornet , Sujeet Pawar , Francesco Stellacci , Henderik W. Frijlink , Anke L.W. Huckriede , Wouter L.J. Hinrichs
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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.</p></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"204 ","pages":"Article 114507"},"PeriodicalIF":4.4000,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0939641124003333/pdfft?md5=4d9f9df06c924b8074f1e7a658edf23a&pid=1-s2.0-S0939641124003333-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Inhibition of influenza virus infection in mice by pulmonary administration of a spray dried antiviral drug\",\"authors\":\"Rick Heida , Paulo H. Jacob Silva , Renate Akkerman , Jill Moser , Jacqueline de Vries-Idema , Aurélien Bornet , Sujeet Pawar , Francesco Stellacci , Henderik W. Frijlink , Anke L.W. Huckriede , Wouter L.J. Hinrichs\",\"doi\":\"10.1016/j.ejpb.2024.114507\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>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. 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Inhibition of influenza virus infection in mice by pulmonary administration of a spray dried antiviral drug
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.
期刊介绍:
The European Journal of Pharmaceutics and Biopharmaceutics provides a medium for the publication of novel, innovative and hypothesis-driven research from the areas of Pharmaceutics and Biopharmaceutics.
Topics covered include for example:
Design and development of drug delivery systems for pharmaceuticals and biopharmaceuticals (small molecules, proteins, nucleic acids)
Aspects of manufacturing process design
Biomedical aspects of drug product design
Strategies and formulations for controlled drug transport across biological barriers
Physicochemical aspects of drug product development
Novel excipients for drug product design
Drug delivery and controlled release systems for systemic and local applications
Nanomaterials for therapeutic and diagnostic purposes
Advanced therapy medicinal products
Medical devices supporting a distinct pharmacological effect.