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

描述(申请人提供)：这个小型企业创新研究第一阶段项目旨在开发一种新型的干粉吸入系统Aktiv-NebTM，用于将抗病毒药物(SiRNAs)粉末输送到婴幼儿的呼吸系统，作为呼吸道感染RSV的干预策略。Alnylam制药公司开发的RSV特异性siRNAs已被证明是有效和特异的，用于RSV感染的体外和体内模型，并在正在进行的人体试验中安全和耐受性良好，重点是鼻腔和气雾剂给药。Aktiv-Dry公司的新型专利粉末产生技术--气泡干燥器二氧化碳辅助雾化(CAN-BD(R))将被用于制造安慰剂和siRNA药物的可吸入粉末(范围在1-5微米之间)。拟议的吸入系统将能够将连续的微粉化干粉气雾剂输送到儿童的呼吸道。Aktiv-NebTM吸入器的性能将基于三个标准来判断：排放的气溶胶尺寸分布、排放剂量在运行持续时间内的一致性以及儿童和婴儿在生理相关呼吸模式下的重复性。该系统将用安慰剂粉末进行校准，并将研究流速、剂量和输送时间对气雾剂产生的影响。优化的吸入系统将应用于经CAN-BD处理的siRNA微粉，并将研究和评估含辅料和不含辅料的配方。第一阶段工作的预期结果是对能够将siRNA粉末输送到呼吸系统的新型干粉吸入系统的可行性进行关键评估。一种安全、有效、稳定和经济的肺部siRNA传递策略将在涉及公共卫生和生物防御的问题上具有巨大的商业应用价值。公共卫生相关性：该项目旨在开发和证明一种新型干粉吸入系统Aktiv-NebTM的可行性，该系统用于将抗病毒药物(SiRNA)粉末输送到幼儿的呼吸系统，作为病毒感染的干预策略。

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.