Department of Biomedical Engineering, Technion - Israel Institute of Technology, Haifa 32000, Israel.
Graduate School of Technology, Industrial and Social Sciences, Tokushima University, Tokushima 770-8506, Japan.
Eur J Pharm Sci. 2019 Sep 1;137:105003. doi: 10.1016/j.ejps.2019.105003. Epub 2019 Jul 11.
Non-spherical particles, and fibers in particular, are potentially attractive airborne carriers for pulmonary drug delivery. Not only do they exhibit a high surface-to-volume ratio relative to spherical aerosols, but their aerodynamic properties also enable them to reach deep into the lungs. Until present, however, our understanding of the deposition characteristics of inhaled aerosols in the distal acinar lung regions has been mostly limited to spheres. To shed light on the fate of elongated aerosols in the pulmonary depths, we explore through in silico numerical simulations the deposition and dispersion characteristics of ellipsoid-shaped fibers in a physiologically-realistic acinar geometry under oscillatory breathing flow conditions mimicking various inhalation maneuvers. The transient translation and rotational movement of micron-sized elongated particles under drag, lift, and gravitational forces are simulated as a function of size (d) and aspect ratio (AR). Our findings underscore how acinar deposition characteristics are intimately linked to the geometrical combination of d and AR under oscillatory flow conditions. Surprisingly, the elongation of the traditionally recommended size range of spherical particles (i.e., 2-3 μm) for acinar deposition may lead to a decrease in deposition efficiency and dispersion. Instead, our findings advocate how elongating particles (i.e., high AR) in the larger size range of 4-6 μm might be leveraged for improved targeted deposition to the acinar regions. Together, these results point to new windows of opportunities in selecting the shape and size of micron-sized fibers for targeted pulmonary deposition. Such in silico efforts represent an essential stepping stone in further exploring aerosol drug carrier designs for inhalation therapy to the deep lungs.
非球形颗粒,尤其是纤维,是潜在的有吸引力的空气传播载体,可用于肺部药物输送。它们不仅具有相对球形气溶胶更高的比表面积,而且其空气动力学特性还使它们能够深入肺部。然而,直到现在,我们对吸入气溶胶在远端腺泡肺部区域的沉积特性的理解主要局限于球形。为了阐明在肺部深处细长气溶胶的命运,我们通过数值模拟方法探索了在模拟各种吸入操作的振荡呼吸流条件下,在生理现实的腺泡几何形状中,椭圆形纤维的沉积和分散特性。模拟了微米级细长颗粒在阻力、升力和重力作用下的瞬态平移和旋转运动,作为尺寸(d)和纵横比(AR)的函数。我们的研究结果强调了在振荡流条件下,腺泡沉积特性与 d 和 AR 的几何组合如何密切相关。令人惊讶的是,传统推荐的用于腺泡沉积的球形颗粒(即 2-3μm)尺寸范围的伸长可能会导致沉积效率和分散性降低。相反,我们的研究结果主张如何利用较大尺寸范围(4-6μm)的伸长颗粒(即高 AR)来提高对腺泡区域的靶向沉积。总之,这些结果为选择用于靶向肺部沉积的微米级纤维的形状和尺寸提供了新的机会。这种计算机模拟努力代表了进一步探索用于肺部深层吸入治疗的气溶胶药物载体设计的重要垫脚石。
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