Kadota Kazunori, Matsumoto Koichi, Uchiyama Hiromasa, Tobita Satoshi, Maeda Munehiro, Maki Daisuke, Kinehara Yuhei, Tachibana Isao, Sosnowski Tomasz R, Tozuka Yuichi
Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
Eur J Pharm Biopharm. 2022 May;174:10-19. doi: 10.1016/j.ejpb.2022.03.010. Epub 2022 Mar 26.
Inhalation therapy can effectively treat chronic obstructive pulmonary disease (COPD), but the physical factors determining the appropriate aerosol delivery into the targeted airways remain unclear. The problem is nontrivial because pulmonary structures differ among individual patients with COPD and depend on the severity of the disease. In an in silico evaluation, the present study investigates the differences in particle transport and deposition in the airways of three patients with different degrees of COPD. Specific pulmonary airway models were reconstructed based on the computed tomography data of three patients with a different degree of COPD severity. The transport and deposition of inhaled particles in the airways were evaluated in a computational fluid dynamics simulation and a Lagrangian multiphase model. The sizes of the inhaled particles (1.0, 2.5, 5.5, 8.5, and 10.0 μm) were representative of drug particles delivered from inhalation devices, including dry powder inhalers (DPIs). The deposition behaviors of the inhaled particles strongly depended on the individual geometrical structure of the airways. The largest inhaled particles (10.0 μm) were most strongly affected by inertia and were deposited mostly in the oropharynx; consequently, they were rare in the bronchi. In contrast, the smallest inhaled particles (1.0 μm) were effectively delivered distally with the airflow. The spatial distributions and amounts of deposited particles in the airways obviously differed among the three COPD patients. Small particles are preferred as they can penetrate the inner lung regions. The results can assist the design and development of powder formulations and DPIs for patients with various severities of COPD.
吸入疗法可有效治疗慢性阻塞性肺疾病（COPD），但决定向目标气道输送合适气雾剂的物理因素仍不明确。这个问题并不简单，因为COPD患者个体的肺部结构不同，且取决于疾病的严重程度。在一项计算机模拟评估中，本研究调查了三名不同程度COPD患者气道内颗粒传输和沉积的差异。基于三名不同COPD严重程度患者的计算机断层扫描数据重建了特定的肺气道模型。在计算流体动力学模拟和拉格朗日多相模型中评估了吸入颗粒在气道内的传输和沉积。吸入颗粒的尺寸（1.0、2.5、5.5、8.5和10.0μm）代表了从吸入装置（包括干粉吸入器（DPI））输送的药物颗粒。吸入颗粒的沉积行为在很大程度上取决于气道的个体几何结构。最大的吸入颗粒（10.0μm）受惯性影响最大，主要沉积在口咽部；因此，它们在支气管中很少见。相比之下，最小的吸入颗粒（1.0μm）随着气流有效地向远端输送。三名COPD患者气道内沉积颗粒的空间分布和数量明显不同。小颗粒更受青睐，因为它们可以穿透肺内部区域。这些结果可为不同严重程度COPD患者的粉末制剂和DPI的设计与开发提供帮助。
