Department of Biomedical Engineering, Technion - Israel Institute of Technology, Haifa 32000, Israel.
Department of Mechanical Engineering, University of Cyprus, 75 Kallipoleos Avenue, P.O. Box 20537 1678, Nicosia, Cyprus.
Eur J Pharm Sci. 2018 Feb 15;113:145-151. doi: 10.1016/j.ejps.2017.09.023. Epub 2017 Sep 20.
It is widely acknowledged that inhaled fibers, e.g. air pollutants and anthropogenic particulate matter, hold the ability to deposit deep into the lungs reaching the distal pulmonary acinar airways as a result of their aerodynamic properties; these particles tend to align with the flow and thus stay longer airborne relative to their spherical counterpart, due to higher drag forces that resist sedimentation. Together with a high surface-to-volume ratio, such characteristics may render non-spherical particles, and fibers in particular, potentially attractive airborne carriers for drug delivery. Until present, however, our understanding of the dynamics of inhaled aerosols in the distal regions of the lungs has been mostly limited to spherical particles. In an effort to unravel the fate of non-spherical aerosols in the pulmonary depths, we explore through numerical simulations the kinematics of ellipsoid-shaped fibers in a toy model of a straight pipe as a first step towards understanding particle dynamics in more intricate acinar geometries. Transient translational and rotational motions of micron-sized ellipsoid particles are simulated as a function of aspect ratio (AR) for laminar oscillatory shear flows mimicking various inhalation maneuvers under the influence of aerodynamic (i.e. drag and lift) and gravitational forces. We quantify transport and deposition metrics for such fibers, including residence time and penetration depth, compared with spherical particles of equivalent mass. Our findings underscore how deposition depth is largely independent of AR under oscillatory conditions, in contrast with previous works where AR was found to influence deposition depth under steady inspiratory flow. Overall, our efforts underline the importance of modeling oscillatory breathing when predicting fiber deposition in the distal lungs, as they are inhaled and exhaled during a full inspiratory cycle. Such physical insight helps further explore the potential of fiber particles as attractive carriers for deep airway targeting.
人们普遍认为，吸入的纤维，例如空气污染物和人为颗粒物，由于其空气动力学特性，能够沉积在肺部深处，到达远端肺泡气道；这些颗粒往往会顺着气流方向排列，因此相对于球形颗粒在空中停留的时间更长，因为它们受到的阻力更大，沉降速度更慢。再加上高的表面积与体积比，这些特性使得非球形颗粒，尤其是纤维，成为潜在有吸引力的药物输送的空气传播载体。然而，直到现在，我们对肺部远端吸入气溶胶的动力学的理解大多仅限于球形颗粒。为了揭示非球形气溶胶在肺部深处的命运，我们通过数值模拟探索了直管道玩具模型中椭圆形纤维的运动学，这是理解更复杂的肺泡几何形状中颗粒动力学的第一步。模拟了微米级椭圆形颗粒的瞬态平移和旋转运动，作为模拟各种吸入动作的层流振荡剪切流的函数，同时还受到空气动力（即阻力和升力）和重力的影响。我们定量比较了这些纤维的输运和沉积指标，包括停留时间和穿透深度，与等效质量的球形颗粒进行比较。我们的发现强调了在振荡条件下，沉积深度在很大程度上与纵横比无关，而之前的研究发现，在稳定吸气流中，纵横比会影响沉积深度。总的来说，我们的努力强调了在预测远端肺部纤维沉积时，对振荡呼吸进行建模的重要性，因为纤维在整个吸气周期中被吸入和呼出。这种物理见解有助于进一步探索纤维颗粒作为有吸引力的深层气道靶向载体的潜力。
