On a model-based approach to improve intranasal spray targeting for respiratory viral infections
Date
2023-05-30
Authors
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
Version
Published version
OA Version
Citation
M.M.H. Akash, Y. Lao, P.A. Balivada, P. Ato, N.K. Ka, A. Mituniewicz, Z. Silfen, J.D. Suman, A. Chakravarty, D. Joseph-McCarthy, S. Basu. "On a model-based approach to improve intranasal spray targeting for respiratory viral infections" Frontiers in Drug Delivery, Volume 3. https://doi.org/10.3389/fddev.2023.1164671
Abstract
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 μm 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.
Description
License
© 2023 Akash, Lao, Balivada, Ato, Ka, Mituniewicz, Silfen, Suman, Chakravarty, Joseph-McCarthy and Basu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.