key: cord-0745214-0x9ptu9g
authors: Basu, S.; Khawaja, U. A.; Rizvi, S. A. A.; Gong, B.; Yeung, W.; Sanchez-Gonzalez, M. A.; Ferrer, G.
title: Evaluation of patient experience for a computationally-guided intranasal spray protocol to augment therapeutic penetration
date: 2021-09-01
journal: nan
DOI: 10.1101/2021.08.31.21262495
sha: 7ed71dd3bd437f0835d9d485fd9150c3e8bf56b4
doc_id: 745214
cord_uid: 0x9ptu9g

The global respiratory outbreak in the form of COVID-19 has underlined the necessity to devise more effective and reproducible intranasal drug delivery modalities, that would also be user-friendly for adoption compliance. In this study, we have collected evaluation feedback from a cohort of 13 healthy volunteers, who assessed two different nasal spray administration techniques, 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 degrees to the vertical, with a vestibular insertion depth of 1.5 cm. The SA protocol is derived from published findings on alternate spray orientations that have been shown to enhance targeted 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% participants opined that the VP technique caused painful irritation. We also tracked the drug transport processes for the two spray techniques in a computed tomography-based nasal reconstruction; the SA protocol marked a distinct improvement in therapeutic penetration when compared to the VP protocol.

The global respiratory outbreak in the form of COVID-19 has underlined the necessity to devise more effective and reproducible intranasal drug delivery modalities, that would also be user-friendly for adoption compliance. In this study, we have collected evaluation feedback from a cohort of 13 healthy volunteers, who assessed two different nasal spray administration techniques, 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 SA protocol is derived from published findings on alternate spray orientations that have been shown to enhance targeted 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% participants opined that the VP technique caused painful irritation. We also tracked the drug transport processes for the two spray techniques in a computed tomography-based nasal reconstruction; the SA protocol marked a distinct improvement in therapeutic penetration when compared to the VP protocol. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

For nasal inflammatory conditions, e.g. chronic rhinosinusitis (CRS), the single mostimportant delivery site for sprayed topical medication is the ostiomeatal complex (or, OMC) 1 as it is the mucociliary drainage pathway and the dominant airflow exchange corridor between the main nasal cavity and the sinus appendages. For viral infections, e.g. SARS-CoV-2, the corresponding pharmaceutic target site during the initial infection phase is the nasopharynx 2-5 , with its tissue-level propensity of angiotensinconverting enzyme 2 (ACE2), a surface receptor that the virus binds to for cell intrusion. Evidence from in silico tracking in digitized medical scan-based geometries and in vitro measurements in 3D-printed anatomic replicas has confirmed 1 that altering nasal spray protocols, e.g. by reorienting the nozzle axis, can often enhance drug delivery by multiple folds, especially for the posterior target sites, like OMC and the nasopharynx. To address the urgency induced by the COVID-19 pandemic for effective yet reproducible intranasal administration techniques, in this study we have tested patient experience for a representative new spray placement technique.

Review Board (IRB) approval. The subjects consented to assessing two different nasal spray placement techniques: (a) "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; (b) "shallow angle" protocol (or, SA), wherein the spray axis is angled at 45° to vertical, with a vestibular insertion depth of 1.5 cm. The SA protocol represents a derivative of the "line-of-sight" (or, LoS) protocol recommended in published findings 1 for CRS management. Figure 1 is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted September 1, 2021. ; https://doi.org/10.1101/2021.08.31.21262495 doi: medRxiv preprint instructions were illustratively communicated (e.g., via Figure 1 (a)-(b)) to the participants, and their feedback was recorded on a sensory attributes' questionnaire.

See Table 1 for the data. Table 1 details the volunteer evaluations for VP and SA protocols. All study participants reported that the SA protocol offered a more gentle and soothing delivery experience, with less impact pressure compared to VP. Furthermore, according to over 60% participants, the VP technique caused painful irritation. Consensus on the SA protocol was that it intranasally provided a comfortable mist-like sensation.

Additionally, the CFD-based trends (see Figure 1 is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted September 1, 2021. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted September 1, 2021. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted September 1, 2021. ; https://doi.org/10.1101/2021.08.31.21262495 doi: medRxiv preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted September 1, 2021. ; https://doi.org/10.1101/2021.08.31.21262495 doi: medRxiv preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted September 1, 2021. ; https://doi.org/10.1101/2021.08.31.21262495 doi: medRxiv preprint

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