Lin Chun-Kai, Hsiao Yuan-Yuan, Nath Pulak, Huang Jen-Huang
Department of Chemical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan.
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan.
Biomicrofluidics. 2019 Aug 7;13(4):044109. doi: 10.1063/1.5121188. eCollection 2019 Jul.
Pulmonary administration is a noninvasive drug delivery method that, in contrast to systemic administration, reduces drug dosage and possible side effects. Numerous testing models, such as impingers and impactors, have previously been developed to evaluate the fate of inhaled drugs. However, such models are limited by the lack of information regarding several factors, such as pulmonary morphology and breathing motion, which are required to fully interpret actual inhaled-drug deposition profiles within the human respiratory tract. In this study, a spontaneous breathing-lung model that integrates branched morphology and deformable alveolar features was constructed using a multilayered fabrication technology to mimic the complex environment of the human lower respiratory tract. The developed model could emulate cyclic and spontaneous breathing motions to inhale and exhale aerosols generated by a nebulizer under diseaselike conditions. Results of this research demonstrate that aerosols (4.2 m) could reach up to the deeper lung regions (generation 19 of the branched lung structure) within the obstructivelike model, whereas lesser penetration (generation 17) was observed when using the restrictivelike model. The proposed breathing-lung model can serve as a testing platform to provide a comprehensive understanding of the pharmacokinetics of pulmonary drugs within the lower lungs.
肺部给药是一种非侵入性给药方法,与全身给药相比,它可减少药物剂量和可能的副作用。以前已经开发了许多测试模型,如冲击器和撞击器,来评估吸入药物的命运。然而,这些模型受到一些因素的限制,如肺部形态和呼吸运动,而这些因素对于充分解释人类呼吸道内实际的吸入药物沉积情况是必需的。在本研究中,利用多层制造技术构建了一个整合分支形态和可变形肺泡特征的自主呼吸肺模型,以模拟人类下呼吸道的复杂环境。所开发的模型可以模拟周期性和自主呼吸运动,在疾病样条件下吸入和呼出雾化器产生的气溶胶。本研究结果表明,在阻塞样模型中,气溶胶(4.2微米)可到达肺部更深区域(分支肺结构的第19代),而在限制样模型中观察到的穿透程度较小(第17代)。所提出的呼吸肺模型可作为一个测试平台,以全面了解肺部药物在下肺部的药代动力学。