Numerical evaluation of spray position for improved nasal drug delivery

• Published in: Scientific reports Vol. 10; no. 1; p. 10568
• Main Authors: Basu, Saikat, Holbrook, Landon T, Kudlaty, Kathryn, Fasanmade, Olulade, Wu, Jihong, Burke, Alyssa, Langworthy, Benjamin W, Farzal, Zainab, Mamdani, Mohammed, Bennett, William D, Fine, Jason P, Senior, Brent A, Zanation, Adam M, Ebert, Jr, Charles S, Kimple, Adam J, Thorp, Brian D, Frank-Ito, Dennis O, Garcia, Guilherme J M, Kimbell, Julia S
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 29.06.2020; Nature Publishing Group UK
• Subjects: Administration, Inhalation; Administration, Intranasal - methods; Betacoronavirus; Computer applications; Computer Simulation; Coronavirus Infections - prevention & control; Coronavirus Infections - virology; Coronaviruses; COVID-19; Drug delivery; Drug Delivery Systems - methods; Humans; Hydrodynamics; Mucosa; Nasal Cavity - anatomy & histology; Nasal Mucosa - drug effects; Nasal Mucosa - virology; Nasal Sprays; Nebulizers and Vaporizers; Pandemics; Pandemics - prevention & control; Paranasal Sinuses - drug effects; Paranasal Sinuses - virology; Pneumonia, Viral - prevention & control; Pneumonia, Viral - virology; SARS-CoV-2; Scintigraphy; Viral Vaccines - administration & dosage
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-66716-0

Topical intra-nasal sprays are amongst the most commonly prescribed therapeutic options for sinonasal diseases in humans. However, inconsistency and ambiguity in instructions show a lack of definitive knowledge on best spray use techniques. In this study, we have identified a new usage strategy for nasal sprays available over-the-counter, that registers an average 8-fold improvement in topical delivery of drugs at diseased sites, when compared to prevalent spray techniques. The protocol involves re-orienting the spray axis to harness inertial motion of particulates and has been developed using computational fluid dynamics simulations of respiratory airflow and droplet transport in medical imaging-based digital models. Simulated dose in representative models is validated through in vitro spray measurements in 3D-printed anatomic replicas using the gamma scintigraphy technique. This work breaks new ground in proposing an alternative user-friendly strategy that can significantly enhance topical delivery inside human nose. While these findings can eventually translate into personalized spray usage instructions and hence merit a change in nasal standard-of-care, this study also demonstrates how relatively simple engineering analysis tools can revolutionize everyday healthcare. Finally, with respiratory mucosa as the initial coronavirus infection site, our findings are relevant to intra-nasal vaccines that are in-development, to mitigate the COVID-19 pandemic.