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

描述（由申请人提供）：该小型企业创新研究I期项目旨在开发一种新型干粉吸入系统Aktiv-NebTM，用于将抗病毒药物（siRNA）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。由Alnylam Pharmaceuticals开发的RSV特异性siRNA已在RSV感染的体外和体内模型中被证明是有效和特异性的，并且在正在进行的专注于鼻内和气雾剂递送的人体试验中是安全和耐受良好的。Aktiv-Dry的新型专利粉末生成技术，CO2辅助雾化与气泡干燥器（CAN-BD（r）），将用于制造安慰剂和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提供一个连续流的微粉化干粉气雾剂进入儿童的呼吸道。将根据三个标准判断Aktiv-NebTM吸入器的性能：释放的气雾剂粒度分布、运行期间释放剂量的一致性以及儿童和婴儿生理相关呼吸模式的再现性。将使用安慰剂粉末对系统进行校准，并研究流速、剂量和给药时间对气雾剂生成的影响。优化的吸入系统将应用于CAN-BD加工的siRNA微粒粉末，并将研究和评价含和不含赋形剂的制剂。第一阶段工作的预期结果是对一种新型干粉吸入系统的可行性进行关键评价，该系统用于将siRNA粉末递送至呼吸系统。一种安全、有效、稳定和经济的siRNA递送至肺部的制剂策略将在与公共卫生和生物防御相关的问题上具有巨大的商业应用。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，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.