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Backgroud The nasal route of targeted drug administration facilitates medical management of chronic and acute onsets of various respiratory conditions such as rhinitis and sinusitis and during the initial onset phase of severe acute respiratory syndrome coronavirus 2, when the infection is still contained within the upper airway. Nevertheless, patient comfort issues that are often associated with intranasal devise usage can lead to low compliance, thereby compromising treatment efficacy. Hence, there is an urgent need to detect reproducible and user-friendly intranasal drug delivery modalities that may promote adoption compliance and yet be effective at targeted transport of drugs to the infective airway regions. Methods In this pilot study, we have collected evaluation feedback from a cohort of 13 healthy volunteers, who used an open-angle swirling effect atomizer to assess two different nasal spray administration techniques (with 0.9% saline solution), namely the vertical placement protocol (or, VP), wherein the nozzle is held vertically upright at a shallow insertion depth of 0.5 cm inside the nasal vestibule; and the shallow angle protocol (or, SA), wherein the spray axis is angled at 45° to the vertical, with a vestibular insertion depth of 1.5 cm. The VP protocol is based on current usage instructions, while the SA protocol is derived from published findings on alternate spray orientations that have been shown to enhance targeted drug delivery at posterior infection sites, e.g., the ostiomeatal complex and the nasopharynx. Results All study participants reported that the SA protocol offered a more gentle and soothing delivery experience, with less impact pressure. Additionally, 60% of participants reported that the VP technique caused painful irritation. We also numerically tracked the drug transport processes for the two spray techniques in a computed tomography-based nasal cavity reconstruction; the SA protocol registered a distinct improvement in airway penetration when compared to the VP protocol. Conclusion The participant-reported unequivocally favorable experience with the new SA protocol justifies a full-scale clinical study aimed at testing the related medication compliance parameters and the corresponding therapeutic efficacies.
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On a model-based approach to improve intranasal spray targeting for respiratory viral infections
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 μ m 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.
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- Award ID(s):
- 2200052
- PAR ID:
- 10460892
- Date Published:
- Journal Name:
- Frontiers in Drug Delivery
- Volume:
- 3
- ISSN:
- 2674-0850
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.3389/fddev.2023.1164671
