Evaluation of Patient Experience for a Computationally-Guided Intranasal Spray Protocol to Augment Therapeutic Penetration: Implications for Effective Treatments for COVID-19, Rhinitis, and Sinusitis
Main Article Content
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.
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.
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.
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.
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
2. Farzal Z, Basu S, Burke A, et al. Comparative study of simulated nebulized and spray particle deposition in chronic rhinosinusitis patients. Paper presented at: International forum of allergy & rhinology 2019.
3. Basu S. Computational characterization of inhaled droplet transport to the nasopharynx. Scientific Reports. 2021;11(1):1-13.
4. Hou YJ, Okuda K, Edwards CE, et al. SARS-CoV-2 reverse genetics reveals a variable infection gradient in the respiratory tract. Cell. 2020;182(2):429-446. e414.
5. Matheson NJ, Lehner PJ. How does SARS-CoV-2 cause COVID-19? Science. 2020;369(6503):510-511.
6. Mittal R, Ni R, Seo J-H. The flow physics of COVID-19. Journal of fluid Mechanics. 2020;894.
7. Basu S, Akash MMH, Hochberg NS, Senior BA, Joseph-McCarthy D, Chakravarty A. From SARS-CoV-2 infection to COVID-19 morbidity: an in silico projection of virion flow rates to the lower airway via nasopharyngeal fluid boluses. Rhinology Online. 2022.
8. Lee IT, Nakayama T, Wu C-T, et al. ACE2 localizes to the respiratory cilia and is not increased by ACE inhibitors or ARBs. Nature communications. 2020;11(1):1-14.
9. Basu S, Akash MMH, Lao Y, et al. A model-based approach to improve intranasal sprays for respiratory viral infections. medRxiv. 2022.
10. Akash MMH, Mituniewicz A, Lao Y, et al. A better way to spray?–a model-based optimization of nasal spray use protocols. Bulletin of the American Physical Society. 2021;66.
11. Treat S, Ebert Jr CS, Farzal Z, et al. Intranasal corticosteroids: patient administration angles and impact of education. 2020.
12. Lao Y, Joseph-McCarthy D, Chakravarty A, et al. Identifying the optimal parameters for sprayed and inhaled drug particulates for intranasal targeting of SARS-CoV-2 infection sites. arXiv preprint arXiv:201016325. 2020.
13. Basu S, Farzal Z, Kimbell JS. ``Magical''fluid pathways: inspired airflow corridors for optimal drug delivery to human sinuses. Paper presented at: APS Division of Fluid Dynamics Meeting Abstracts2017.
14. Meltzer EO, Bardelas J, Goldsobel A, Kaiser H. A preference evaluation study comparing the sensory attributes of mometasone furoate and fluticasone propionate nasal sprays by patients with allergic rhinitis. Treatments in respiratory medicine. 2005;4(4):289-296.
15. Bachert C, El-Akkad T. Patient preferences and sensory comparisons of three intranasal corticosteroids for the treatment of allergic rhinitis. Annals of Allergy, Asthma & Immunology. 2002;89(3):292-297.
16. Stokes M, Amorosi SL, Thompson D, Dupclay L, Garcia J, Georges G. Evaluation of patients' preferences for triamcinolone acetonide aqueous, fluticasone propionate, and mometasone furoate nasal sprays in patients with allergic rhinitis. Otolaryngology—Head and Neck Surgery. 2004;131(3):225-231.
17. Khanna P, Shah A. Assessment of sensory perceptions and patient preference for intranasal corticosteroid sprays in allergic rhinitis. American journal of rhinology. 2005;19(3):316-321.
18. Ferrer G, Sanchez-Gonzalez MA. Effective Nasal Disinfection as an Overlooked Strategy in Our Fight against COVID-19. Ear, Nose & Throat Journal. 2021:01455613211002929.
19. Lee P-I, Hsueh P-R. Emerging threats from zoonotic coronaviruses-from SARS and MERS to 2019-nCoV. Journal of microbiology, immunology, and infection. 2020;53(3):365.
20. Benninger MS, Hadley JA, Osguthorpe JD, et al. Techniques of intranasal steroid use. Otolaryngology-Head and Neck Surgery. 2004;130(1):5-24.
21. Gungor AA. The aerodynamics of the sinonasal interface: the nose takes wing-a paradigm shift for our time. Int Forum Allergy Rhinol. 2013;3(4):299-306.
22. Basu S, Frank‐Ito DO, Kimbell JS. On computational fluid dynamics models for sinonasal drug transport: Relevance of nozzle subtraction and nasal vestibular dilation. International journal for numerical methods in biomedical engineering. 2018;34(4):e2946.
23. AT Borojeni A, Frank‐Ito DO, Kimbell JS, Rhee JS, Garcia GJ. Creation of an idealized nasopharynx geometry for accurate computational fluid dynamics simulations of nasal airflow in patient‐specific models lacking the nasopharynx anatomy. International journal for numerical methods in biomedical engineering. 2017;33(5):e2825.
24. Basu S, Witten N, Kimbell J. Influence of localized mesh refinement on numerical simulations of post-surgical sinonasal airflow. Paper presented at: Journal of aerosol medicine and pulmonary drug delivery2017.
25. Wilhelm FH, Roth WT, Sackner MA. The LifeShirt: an advanced system for ambulatory measurement of respiratory and cardiac function. Behavior Modification. 2003;27(5):671-691.
26. Tay SY, Chao SS, Mark KTT, Wang DY. Comparison of the distribution of intranasal steroid spray using different application techniques. Paper presented at: International forum of allergy & rhinology2016.
27. Laube BL. Devices for aerosol delivery to treat sinusitis. Journal of aerosol medicine. 2007;20(s1):S5-S18.