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重要方法，目前正在开发用于许多其他疾病的方法。然而，目前还不存在允许吸入药物在肺部特定的靶向区域沉积的方法，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。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，这种激进的方法将允许非磁性药物在肺部进行非侵入性靶向治疗，这是以前从未实现的。此外，如果能够在实验室工作台上很容易地测试通过口腔咽喉进入肺部的药物的量，那么新的或改进的吸入气雾剂药物的开发将得到极大的帮助。虽然吸入器测试设备的全球主要供应商现在销售我们为此目的在成人身上开发的设备，但从来没有严格开发过用于儿童或婴儿气雾剂药物输送的工具。在目前的应用中，我们建议创建理想化的儿童口腔和鼻腔呼吸道的复制品。这将使儿童用医用气雾剂的未来发展和优化成为可能。由于儿童的呼吸障碍也被认为会引起颅面结构的改变，我们打算对呼吸障碍引起的颅面异常的儿童受试者的复制品中的气溶胶沉积进行表征，以确定其对此类患者肺部药物输送的影响。这在确定是否需要为这些患者群体开发不同的理想化儿童几何形状方面将是重要的。最后，还将开发用于优化使用替代气体(氦-氧)的吸入性气雾剂治疗的数学模型，以改善对严重呼吸窘迫患者的气雾剂输送。本申请中提出的研究涉及吸入性气雾剂的力学方面的开创性方面，并将改进治疗性气雾剂药物输送的未来发展。

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.