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 ' siallyllactosamine-functionalized (3-cyclodextrin (CD-6 ' SLN) ' 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 ' 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 ' SLN using an aerosol generator that allowed for the controlled administration of powder formulations to the lungs of mice. CD-6 ' SLN ' 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 ' 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.