Mechanics of Inhaled Aerosols

将医用气溶胶输送到呼吸道中是治疗呼吸系统疾病（如哮喘）的重要方法，并且正在开发用于许多其他疾病。然而，目前还没有允许吸入药物存款在肺的特定靶向区域的方法，尽管我们和其他人先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，在本申请中，我们提出使用超声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侵入性靶向肺部的抗肿瘤药物，这是以前从未实现过的。此外，如果能在实验室工作台上容易地测试通过口-喉进入肺部的药物量，将大大有助于新的或改进的吸入气雾剂药物的开发。虽然全球主要的吸入器测试设备供应商现在销售我们为此目的开发的成人设备，但尚未严格开发用于儿童或婴儿气雾剂药物输送的此类工具。在本申请中，我们提出创建口腔和鼻气道的理想化儿科复制品。这将允许未来开发和优化用于儿童的医用气雾剂。由于儿童呼吸系统疾病也被认为会引起颅面结构的变化，因此我们打算表征呼吸系统疾病引起颅面异常的儿科受试者的复制品中的气溶胶沉积，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化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解决了吸入气雾剂的力学中的突破性方面，并且将允许治疗性气雾剂药物递送的改进的未来发展。

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.