Mechanics of Inhaled Aerosols

将医用气雾剂输送到呼吸道是治疗哮喘等呼吸系统疾病的一种重要方法，许多其他疾病也在开发中。然而，尽管我们和其他人之前的工作已经证明了磁性颗粒的靶向性，但目前还没有一种方法可以让吸入的药物沉积在肺部的特定靶向区域。不幸的是，很少有药物具有磁性。相反，在目前的应用中，我们建议使用超声波来控制吸入的气溶胶颗粒的运动。如果成功，这种激进的方法将使肺部非磁性药物的非侵入性靶向成为可能，这是以前从未实现过的。此外，如果能在实验室的工作台上方便地测试通过口腔咽喉进入肺部的药物量，将大大有助于开发新的或改进的吸入性气溶胶药物。虽然全球主要的吸入器测试设备供应商现在销售一种由我们开发的用于成人的设备，但从未严格开发过用于儿童或婴儿气溶胶药物输送的此类工具。在目前的应用中，我们建议创建理想的口腔和鼻气道的儿科复制品。这将允许未来开发和优化用于儿童的医用气溶胶。由于儿童呼吸系统疾病也被认为会引起颅面结构的变化，我们打算在呼吸系统疾病引起颅面异常的儿童受试者的复制品中表征气溶胶沉积，以确定其对此类患者肺部药物输送的影响。这对于确定是否需要为这些患者群体开发不同的理想儿童几何形状将是重要的。最后，还将开发用于优化使用替代气体（氦氧）的吸入气溶胶治疗的数学模型，以改善严重呼吸窘迫患者的气溶胶输送。在本申请中提出的研究解决了吸入气雾剂力学的突破性方面，并将允许改善治疗性气雾剂药物递送的未来发展。

The delivery of medical aerosols into the respiratory tract is an important method of treating respiratory diseases such as asthma, and is under development for many other diseases. However, at present, no method exists that allows inhaled drug to deposit in a specific, targeted region of the lungs, although previous work by us, and others, has demonstrated targeting of magnetic particles. Unfortunately, few drugs are magnetic. Instead, in the present application, we propose to use ultrasound to control the motion of inhaled aerosol particles. If successful, this radical approach would allow noninvasive targeting of nonmagnetic drugs in the lungs, something that has never been achieved previously. In addition, the development of new or improved inhalation aerosol drugs would be greatly aided if the amount of drug delivered past the mouth-throat into the lungs could be easily tested on the laboratory benchtop. While the major worldwide supplier of inhaler testing equipment now sells a device developed by us for this purpose in adults, no such tool has ever been rigorously developed for delivery of aerosol drugs in children or infants. In the present application, we propose to create idealized pediatric replicas of the oral and nasal airways. This will allow the future development and optimization of medical aerosols for use in children. Because respiratory disorders in children are also thought to cause changes in craniofacial structure, we intend to characterize aerosol deposition in replicas of pediatric subjects with craniofacial abnormalities brought on by respiratory disorders in order to determine its effect on drug delivery to the lungs in such patients. This will be important in determining whether different idealized child geometries need to be developed for these patient populations. Finally, mathematical models for use in optimizing inhaled aerosol therapy using alternative gases (helium-oxygen) will also be developed for improving aerosol delivery to patients with severe respiratory distress. The research proposed in the present application addresses groundbreaking aspects in the mechanics of inhalation aerosols and will allow improved future development of therapeutic aerosol drug delivery.