Aktiv-Neb: A Dry Powder Inhaler for Anti-RSV siRNA Microparticles

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DESCRIPTION (provided by applicant): This Small Business Innovation Research Phase I project aims to develop a novel dry powder inhalation system, Aktiv-NebTM, for delivering antiviral drug (siRNAs) powders, to the respiratory systems of infants and young children as an intervention strategy for respiratory infection RSV. RSV-specific siRNAs developed by Alnylam Pharmaceuticals, have been demonstrated to be efficacious and specific using in vitro and in vivo models of RSV infection and safe and well tolerated in ongoing human trials focused on intranasal and aerosol delivery. Aktiv-Dry's novel, patented powder generating technology, CO2-assisted nebulization with a bubble dryer (CAN-BD(r)), will be applied to make inhalable powders of placebo and siRNA drugs (ranging between 1- 5 microns). The proposed inhalation system will be capable of delivering a continuous stream of micronized dry powder aerosol into the respiratory tract of children. The performance of Aktiv-NebTM inhaler will be judged based on three criteria; the emitted aerosol size distribution, the consistency of emitted dose over the duration of run, and the reproducibility at physiologically relevant breathing patterns for children and infants. The system will be calibrated with placebo powders and the effect of flow rates, dosage, and delivery time on the aerosol generation will be studied. The optimized inhalation system will be applied to CAN-BD processed siRNA microparticle powders and formulations with and without excipients will be studied and evaluated. The expected outcome of the Phase I effort is a critical evaluation on the feasibility of a novel dry powder inhalation system, for enabling the delivery of siRNA powders, to the respiratory system. A safe, effective, stable, and economical formulation strategy for siRNA delivery to the lungs would have tremendous commercial applications for issues related to public health and biodefense. PUBLIC HEALTH RELEVANCE: The project aims to develop and demonstrate the feasibility of a novel dry powder inhalation system, Aktiv-NebTM, for delivering antiviral drug (siRNA) powders to the respiratory systems of young children as an intervention strategy for viral infection.