A model-based approach to improve intranasal sprays for respiratory viral infections
Saikat Basu, Mohammad Mehedi Hasan Akash, Yueying Lao, Pallavi A Balivada, Phoebe Ato, Nogaye K Ka, Austin Mituniewicz, Zachary Silfen, Julie Suman, Arijit Chakravarty, Diane Joseph-Mccarthy
doi:10.1101/2022.01.26.22269854
Drug delivery for viral respiratory infections, such as SARS-CoV-2, can be enhanced significantly by targeting the nasopharynx, which is the dominant initial infection site in the upper airway, for example by nasal sprays. However, under the standard recommended spray usage protocol ("Current Use", or CU), the nozzle enters the nose almost vertically, resulting in sub-optimal deposition of drug droplets at the nasopharynx. Using computational fluid dynamics simulations in two anatomic nasal geometries, along with experimental validation of the generic findings in a different third subject, we have identified a new "Improved Use" (or, IU) spray protocol. It entails pointing the spray bottle at a shallower angle (almost horizontally), aiming slightly toward the cheeks. We have simulated the performance of this protocol for conically injected spray droplet sizes of 1 -24 µm, at two breathing rates: 15 and 30 L/min. The lower flowrate corresponds to resting breathing and follows a viscouslaminar model; the higher rate, standing in for moderate breathing conditions, is turbulent and is tracked via Large Eddy Simulation. The results show that (a) droplets sized between ∼ 6 -14 µm are most efficient at direct landing over the nasopharyngeal viral infection hot-spot; and (b) targeted drug delivery via IU outperforms CU by approximately 2 orders-of-magnitude, under the two tested inhalation conditions. Also quite importantly, the improved delivery strategy, facilitated by the IU protocol, is found to be robust to small perturbations in spray direction, underlining the practical utility of this simple change in nasal spray administration protocol.
Author contributions SB, DJM, AC conceived this study; SB developed the study protocol, the anatomic reconstructions and drafted the manuscript; MMHA carried out the physical experiments and the theoretical analysis; SB, YL, PAB, PA, NKK performed the numerical simulations; AM, ZS processed the computational data; JS tested the overthe-counter spray products; SB and DJM jointly supervised the student researchers (MMHA, YL, PAB, PA, NKK, AM, ZS).
Conflicts of interest The authors declare no competing interests.
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