Akash Mohammad Mehedi Hasan, Lao Yueying, Balivada Pallavi A, Ato Phoebe, Ka Nogaye K, Mituniewicz Austin, Silfen Zachary, Suman Julie D, Chakravarty Arijit, Joseph-McCarthy Diane, Basu Saikat
Department of Mechanical Engineering, South Dakota State University, Brookings, SD, United States.
Department of Biomedical Engineering, Boston University, Boston, MA, United States.
Front Drug Deliv. 2023 May 30;3:1164671. doi: 10.3389/fddev.2023.1164671. eCollection 2023.
The nasopharynx, at the back of the nose, constitutes the dominant initial viral infection trigger zone along the upper respiratory tract. However, as per the standard recommended usage protocol ("Current Use", or CU) for intranasal sprays, the nozzle should enter the nose almost vertically, resulting in sub-optimal nasopharyngeal drug deposition. Through the Large Eddy Simulation technique, this study has replicated airflow under standard breathing conditions with 15 and 30 L/min inhalation rates, passing through medical scan-based anatomically accurate human airway cavities. The small-scale airflow fluctuations were resolved through use of a sub-grid scale Kinetic Energy Transport Model. Intranasally sprayed droplet trajectories for different spray axis placement and orientation conditions were subsequently tracked via Lagrangian-based inert discrete phase simulations against the ambient inhaled airflow field. Finally, this study verified the computational projections for the upper airway drug deposition trends against representative physical experiments on sprayed delivery performed in a 3D-printed anatomic replica. The model-based exercise has revealed a new "Improved Use" (or, IU) spray usage protocol for viral infections. It entails pointing the spray bottle at a shallower angle (with an almost horizontal placement at the nostril), aiming slightly toward the cheeks. From the conically injected spray droplet simulations, we have summarily derived the following inferences: (a) droplets sized between 7-17 m are relatively more efficient at directly reaching the nasopharynx via inhaled transport; and (b) with realistic droplet size distributions, as found in current over-the-counter spray products, the targeted drug delivery through the IU protocol outperforms CU by a remarkable 2 orders-of-magnitude.
鼻咽位于鼻腔后部,是上呼吸道主要的初始病毒感染触发区域。然而,根据鼻喷雾剂的标准推荐使用方案(“当前使用”,即CU),喷嘴应几乎垂直进入鼻腔,导致鼻咽部药物沉积效果欠佳。本研究通过大涡模拟技术,在标准呼吸条件下,以15升/分钟和30升/分钟的吸入速率,模拟气流通过基于医学扫描的解剖学精确的人体气道腔。通过使用亚网格尺度动能传输模型解决了小尺度气流波动问题。随后,通过基于拉格朗日的惰性离散相模拟,针对周围吸入气流场,跟踪不同喷雾轴放置和方向条件下鼻内喷雾液滴的轨迹。最后,本研究针对在3D打印解剖复制品上进行的喷雾给药代表性物理实验,验证了上呼吸道药物沉积趋势的计算预测。基于模型的实验揭示了一种针对病毒感染的新的“改进使用”(即IU)喷雾使用方案。该方案要求将喷雾瓶以较浅的角度(在鼻孔处几乎水平放置)指向,略微朝向脸颊。从锥形喷射喷雾液滴模拟中,我们总结得出以下推论:(a)7-17微米大小的液滴通过吸入传输直接到达鼻咽部的效率相对更高;(b)对于目前非处方喷雾产品中实际的液滴尺寸分布,通过IU方案进行的靶向药物递送比CU方案的效果显著高出2个数量级。