Department of Mechanical Engineering, University of Alberta, Edmonton, Alberta, Canada.
J Aerosol Med Pulm Drug Deliv. 2013 Feb;26(1):31-40. doi: 10.1089/jamp.2011.0921. Epub 2012 May 2.
Aerosolized chemotherapy has been recognized as a potential treatment for lung cancer. The challenge of providing sufficient therapeutic effects without reaching dose-limiting toxicity levels hinders the development of aerosolized chemotherapy. This could be mitigated by increasing drug-delivery efficiency with a noninvasive drug-targeting delivery method. The purpose of this study is to use direct numerical simulations to study the resulting local enhancement of deposition due to magnetic field alignment of high aspect ratio particles.
High aspect ratio particles were approximated by a rigid ellipsoid with a minor diameter of 0.5 μm and fluid particle density ratio of 1,000. Particle trajectories were calculated by solving the coupled fluid particle equations using an in-house micro-macro grid finite element algorithm based on a previously developed fictitious domain approach. Particle trajectories were simulated in a morphologically realistic geometry modeling a symmetrical terminal bronchiole bifurcation. Flow conditions were steady inspiratory air flow due to typical breathing at 18 L/min. Deposition efficiency was estimated for two different cases: [1] particles aligned with the streamlines and [2] particles with fixed angular orientation simulating the magnetic field alignment of our previous in vitro study.
The local enhancement factor defined as the ratio between deposition efficiency of Case [1] and Case [2] was found to be 1.43 and 3.46 for particles with an aspect ratio of 6 and 20, respectively.
Results indicate that externally forcing local alignment of high aspect ratio particles can increase local deposition considerably.
雾化化疗已被认为是治疗肺癌的一种潜在方法。提供足够的治疗效果而又不达到剂量限制毒性水平的挑战阻碍了雾化化疗的发展。通过使用非侵入性的药物靶向输送方法来提高药物输送效率，可以减轻这种情况。本研究的目的是使用直接数值模拟来研究由于高纵横比颗粒的磁场对准而导致的局部沉积增强。
高纵横比颗粒通过具有 0.5 μm 小直径和 1000 的流体颗粒密度比的刚性椭球体来近似。使用基于先前开发的虚构域方法的内部微-宏网格有限元算法，通过求解耦合的流体颗粒方程来计算颗粒轨迹。使用模拟对称终末细支气管分叉的形态学上逼真的几何形状来模拟颗粒轨迹。流动条件是典型呼吸时 18 L/min 的稳定吸气气流。为两种不同情况估计了沉积效率：[1] 与流线对齐的颗粒和 [2] 模拟我们先前体外研究中磁场对准的固定角取向的颗粒。
定义为情况 [1] 和情况 [2] 沉积效率之比的局部增强因子分别为 6 和 20 纵横比颗粒的 1.43 和 3.46。
结果表明，外部强制局部对准高纵横比颗粒可以大大增加局部沉积。
