论文标题

识别用于喷涂和吸入药物颗粒的最佳参数,用于SARS-COV-2感染部位的鼻内靶向

Identifying the optimal parameters for sprayed and inhaled drug particulates for intranasal targeting of SARS-CoV-2 infection sites

论文作者

Lao, Yueying, Joseph-McCarthy, Diane, Chakravarty, Arijit, Balivada, Pallavi A., Ato, Phoebe, Ka, Nogaye K., Basu, Saikat

论文摘要

通过靶向鼻咽,可以显着增强Covid-19处理的功效,这已被证明是SARS-COV-2的主要初步感染部位。尽管鼻内药物可以通过滴剂或喷雾轻松施用,但很难测试当前方案是否会始终如一地将适量的药物输送到该位置。我们有兴趣开发一种硅原型制作工具,以快速识别鼻内递送的最佳参数。在这项研究中,我们应用了计算流体动力学来模拟流体流经鼻腔的流动,并检查了药物制剂的颗粒沉积,模仿了不同的递送方法。使用数字化和网状计算机断层扫描(CT)扫描人类患者得出鼻几何模型。使用鼻几何形状,我们模拟了两个不同的气流:以15 LPM(升/分钟)的层状模型模拟静息呼吸速率和用于实现30 LPM的较高流速的大型涡流模拟(LES)模型。我们能够为这两个气流方案运行粒子跟踪模拟,以测试不同的药物特性,例如粒径。所使用的不同注射方法包括表面注射,最能将基于吸入器的颗粒液滴释放到鼻孔中,并最能将喷雾剂复制到鼻孔中的锥体注入方法。该研究的结果表明,针对鼻内感染部位的最佳药物粒径约为6-14微米。

Efficacy for COVID-19 treatments can be enhanced significantly through targeting the nasopharynx, which has been shown to be the dominant preliminary infection site for SARS-CoV-2. Although intranasal drugs can be administered easily through drops or sprays, it is difficult to test whether current protocols will deliver the right amount of the drug to this location consistently. We are interested in developing an in silico prototyping tool to rapidly identify optimal parameters for intranasal delivery. In this study, we have applied computational fluid dynamics to simulate fluid flow through the nasal cavity and examined particle deposition for a drug formulation, mimicking different delivery methods. The nasal geometry models were derived using digitized and meshed computed tomography (CT) scans of human patients. Using the nasal geometries, we simulated two different airflows: a laminar model at 15 LPM (Liters/min) that simulated resting breathing rate and a Large Eddy Simulation (LES) model used to achieve a higher flow rate of 30 LPM. We were able to run particle tracking simulations for these two airflow schemes to test different drug properties such as particle size. The different injection methods used include surface injection which best replicates an inhaler-based release of particle droplets into the nostril and the cone injection method which best replicates a spray into the nostril. The results of the study suggest that the most optimal drug particle size for targeting the intranasal infection sites is around 6-14 microns.

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