Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, Delaware, USA.
School of Chemical Engineering, Oklahoma State University, Stillwater, Oklahoma, USA.
J Aerosol Med Pulm Drug Deliv. 2021 Feb;34(1):42-56. doi: 10.1089/jamp.2019.1564. Epub 2020 Jul 14.
Delivery of aerosols to isolated lobes of the lungs would be beneficial for diseases that have lobe-specific effects, such as cancer, pneumonia, and chronic obstructive pulmonary disorder. Recent computational fluid-particle dynamic (CFPD) modeling has demonstrated that in low flow rates, the inlet location of a particle at the mouth dictates the lobe into which it will deposit. However, realization of this lobe-specific deposition has yet to be attempted experimentally or in the clinic. To address this, we sought to develop a proof-of-concept model and targeting device for achieving lobe-specific delivery. Using 3D printing, a lung replica was created from a computed tomography scan of a healthy 47-year-old male volunteer and connected to a flow setup to control inlet flow rate and outlet airflow distribution to each lobe. A device was designed and fabricated that directs particles to an inlet location that is 5% of the total inlet area and described by radial coordinates (,). Filter paper at sampling ports for each lobe was used to capture fluorescent polystyrene particles to quantify particle collection. We evaluated lobe-specific targeting at varied inlet coordinates, particle diameters, inlet flow rates, and disease lobe flow rate distribution profiles. Guided by CFPD modeling, inlet locations were identified that increased particle collection to a target lobe between 63% and 90%. For example, release of fluorescent particles at the inlet location = 4.67 mm, = 252° with respect to the center of the inlet using 1 μm particles, 1 L/min inlet flow rate, and healthy subject lobe flow distribution profile yielded 90% of the aerosol dose to the right upper lobe, corresponding to an increase of 4.6 × above the non-targeted percent particle collection. Particle size, inlet flow rate, and disease airflow distributions were all shown to generally decrease the efficiency of lobe-specific targeting. Our results indicate that aerosol targeting of a specific lobe is possible under optimized conditions and that controlling inlet locations could be a potentially useful method for treatment of lobe-specific diseases. This is the first demonstration of lobe-specific particle collection in a physical lung model and illuminates numerous challenges that will be faced as this method is translated to clinical applications.
将气雾剂输送到肺部的孤立叶区对于具有叶特异性效应的疾病（如癌症、肺炎和慢性阻塞性肺疾病）将是有益的。最近的计算流体-颗粒动态（CFPD）模型表明，在低流速下，颗粒在口中的入口位置决定了它将沉积到哪个叶区。然而，这种叶特异性沉积的实现尚未在实验或临床中尝试过。为了解决这个问题，我们试图开发一种用于实现叶特异性输送的概念验证模型和靶向装置。使用 3D 打印，从一位 47 岁健康男性志愿者的计算机断层扫描创建了肺模型，并将其连接到流量设置，以控制每个叶区的入口流量和出口气流分布。设计并制造了一种装置，该装置将颗粒引导到占总入口面积 5%的入口位置，并通过径向坐标（，）来描述。每个叶区的采样端口的滤纸用于捕获荧光聚苯乙烯颗粒以量化颗粒收集。我们评估了在不同入口坐标、颗粒直径、入口流速和疾病叶区流速分布下的叶特异性靶向。在 CFPD 模型的指导下，确定了增加目标叶区颗粒收集的入口位置，范围在 63%到 90%之间。例如，使用 1μm 颗粒、1L/min 入口流速和健康受试者叶区流速分布，在入口位置 = 4.67 mm、 = 252°相对于入口中心释放荧光颗粒，导致 90%的气溶胶剂量输送到右上叶区，比非靶向的颗粒收集百分比增加了 4.6 倍。颗粒大小、入口流速和疾病气流分布都显示出通常会降低叶特异性靶向的效率。我们的结果表明，在优化条件下，特定叶区的气溶胶靶向是可能的，并且控制入口位置可能是治疗叶特异性疾病的一种很有前途的方法。这是首次在物理肺模型中证明了叶特异性颗粒收集，并阐明了在将这种方法转化为临床应用时将面临的许多挑战。
