On a model-based approach to improve intranasal spray targeting for respiratory viral infections
Mohammad Mehedi Hasan Akash, Yueying Lao, Pallavi A Balivada, Phoebe Ato, Nogaye K Ka, Austin Mituniewicz, Zachary Silfen, Julie D Suman, Arijit Chakravarty, Diane Joseph-Mccarthy, Saikat Basu
Frontiers in Drug Delivery, doi:10.3389/fddev.2023.1164671
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 suboptimal 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.
Ethics statement The studies involving human participants were reviewed and approved by The use of the archived and anonymized medical records was approved with exempt status by the Institutional Review Board (IRB) of the University of North Carolina (UNC) at Chapel Hill, with the requirement of informed consent waived for retrospective use in computational research. The patients/ FIGURE 10 A demonstrative artistic rendering for the side view during "Improved Use" (IU) protocol, outlining how to ideally hold a spray bottle during intranasal administration with one's head tilted slightly forward. g points to the direction of gravity. Rendering is courtesy of the corresponding author. participants provided their written informed consent to participate in this study.
Author contributions MA: experiments, data analysis, and writing; YL: digital reconstructions and simulations; PB: simulations and data analysis; PA: simulations and data analysis; NK: simulations and data analysis; AM: data analysis; ZS: data analysis; JS: spray testing and writing; AC: conceptualization, study design and data analysis input, writing; DJ-M: conceptualization and project administration; SB: conceptualization, study design, funding acquisition, project administration, digital reconstructions, numerical simulations, theoretical calculations, data analysis, and writing.
Conflict of interest Author JS was employed by the Aptar Pharma. Author AC was employed by Fractal Therapeutics. The..
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'abstract': '<jats:p>The nasopharynx, at the back of the nose, constitutes the dominant initial viral '
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'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\xa0L/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 '
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'7–17\xa0<jats:italic>μ</jats:italic>m are relatively more efficient at directly reaching the '
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