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.

No abstract

For sinus diseases, targeted delivery at affected sinonasal sites can be the key to improve efficacy of topical sprays as a nasal therapeutic. Considering that ostiomeatal complex (OMC) is the mucociliary drainage pathway and airflow exchange corridor between the main airway and the frontal, maxillary, and anterior ethmoid sinuses, we have identified sprayer techniques that are more effective in targeting OMC, along with the sinus cavities. Nasal airflow and drug transport have been numerically simulated in five CT-based sinonasal airway reconstructions, drawn from pre-operative chronic rhinosinusitis patients. In each digital model, we applied two different spray orientations at 5-mm insertion: (a) package insert-based direction -an upright spray axis with subject-head inclined slightly forward (22.5 • ), (b) line-of-sight (LoS) -with spray axis directed at OMC and through centroid of visible OMC's projection on the view-plane for best OMC-sighting. LoS protocol registered an average 8-fold higher targeted delivery, with the finding supported by both parametric t-test and non-parametric Wilcoxon signed rank test. Simulated dose in two representative models was validated by in vitro spray experiments in 3D-printed replicas. Finally, observational LoS scores, based on how much of OMC was visible from nostrils, correlated well with the ratio of the projected area of the OMC on the nostril plane to the area of the nostril plane itself. While these CFD-based findings can eventually translate into new personalized spray usage instructions and change the standard-ofcare for nasal treatments, this study also demonstrates how use of relatively simple engineering tools can revolutionize everyday healthcare.