Abstract

Central Nervous System (CNS) disorders are one of the major causes of fatalities in the world today. Thus, it is essential to transport a considerable amount of drugs to a specific brain location for any treatment to be effective. A noninvasive approach is direct nanodrug delivery via the nasal route. The main pathway for these drugs into the brain requires crossing the Blood-Brain Barrier (BBB), located along the olfactory region of the nasal cavity. Tight junctions of the BBB allow only nanoparticles of sufficiently high concentrations to pass through. Multifunctional nanoparticles can be used to target the brain via the olfactory bulb. Computational Fluid-Particle Dynamics (CF-PD) simulations offer a manageable, accurate and cost-effective route for studying this possibility. For the present study, the open-source CFD toolbox OpenFOAM was employed to conduct all fluid-particle dynamics simulations. Previous studies have shown that normal injection of particles through the nostrils have shown clinically insignificant amounts of olfactory deposition. The main objective of this study is to utilize the Particle Release Map (PRM) methodology to optimize the nanodrug deposition efficiency inside the olfactory region, using a representative human nasal cavity as a test bed. While published results indicate maximum olfactory depositions of 3 to 4% (for 1 nm particles) under normal breathing rate, the PRM approach achieves 28.4% deposition for 10 nm and 8.7% for 100 nm particles in the olfactory bulb. Practically, such elevated olfactory depositions with the PRM technique could be achieved in conjunction with a well-placed nasal cannula.

Copyright © 2021 American Association for Aerosol Research

摘要

中枢神经系统 (CNS) 疾病是当今世界上导致死亡的主要原因之一。因此，为了使任何治疗有效，必须将大量药物运送到特定的大脑位置。一种非侵入性方法是通过鼻腔途径直接递送纳米药物。这些药物进入大脑的主要途径需要穿过位于鼻腔嗅觉区域的血脑屏障 (BBB)。BBB 的紧密连接只允许足够高浓度的纳米粒子通过。多功能纳米粒子可用于通过嗅球瞄准大脑。计算流体粒子动力学 (CF-PD) 模拟为研究这种可能性提供了一种可管理、准确且具有成本效益的途径。对于目前的研究，开源 CFD 工具箱 OpenFOAM 用于进行所有流体粒子动力学模拟。先前的研究表明，通过鼻孔正常注射颗粒已显示出临床上微不足道的嗅觉沉积量。本研究的主要目的是利用粒子释放图 (PRM) 方法优化嗅觉区域内的纳米药物沉积效率，使用具有代表性的人类鼻腔作为试验床。虽然已发表的结果表明在正常呼吸频率下最大嗅觉沉积为 3% 到 4%（对于 1 nm 颗粒），但 PRM 方法在嗅球中实现了 28.4% 的 10 nm 沉积和 8.7% 的 100 nm 颗粒沉积。实际上，这种通过 PRM 技术提高的嗅觉沉积可以与放置良好的鼻插管结合使用。

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