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Optimized gravity-driven intranasal drop administration delivers significant doses to the ostiomeatal complex and maxillary sinus

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Abstract

Chronic and allergic rhinosinusitis impacts approximately 12% of the global population. Challenges in rhinosinusitis treatment include paranasal sinus inaccessibility and variability in delivery efficiency among individuals. This study addresses these challenges of drug delivery by developing a high-efficiency, low-variability protocol for nasal drop delivery to the ostiomeatal complex (OMC) and maxillary sinus. Patient-specific nasal casts were dissected to reveal the configurations of conchae and meatus, providing insights into anatomical features amendable for sinus delivery. Fluorescent dye-enhanced videos visualized the dynamic liquid translocation in transparent nasal casts, allowing real-time assessment and quick adjustment to delivery parameters. Dosimetry to the OMC and maxillary sinus were quantified as drop count and mass using a precision scale. Key delivery factors, including the device type, formulation, and head-chin orientation, were systematically investigated in a cohort of ten nasal casts. Results show that both the squeeze bottle and soft-mist nasal pump yielded notably low doses to the OMC with high variability, and no dose from these two devices was detected within the maxillary sinuses. In contrast, the proposed approach, which included a curved nozzle surpassing the nasal valve and leveraged gravity-driven liquid translocation along the lateral nasal wall, delivered significant doses to the OMC and maxillary sinus. Iterative experimentations identified the optimal head tilt to be 40° and chin tilt to be° from the lateral recumbent position. Statistical analyses established the drop count required for effective OMC/sinus delivery. The proposed delivery protocol holds the potential to enhance chronic rhinosinusitis treatment outcomes with low variability. The dual role of nasal anatomy in posing challenges and offering opportunities highlights the need for future investigations using diverse formulations in a larger cohort of nasal models.

Graphical Abstract

Optimized gravity-driven intranasal drop administration delivers significant doses to the ostiomeatal complex and maxillary sinus.

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Availability of data and materials

The datasets generated during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

Dr. Chantal Darquenne at UCSD and Dr. Richard Corley at Greek Creek Toxicokinetics Consulting were gratefully acknowledged for sharing the M2 nasal model used in this study.

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Authors and Affiliations

  1. Department of Biomedical Engineering, University of Massachusetts, 1 University Ave., Falmouth Hall 302I, Lowell, MA, 01854, USA

    Amr Seifelnasr & Jinxiang Xi

  2. Department of Mechanical Engineering, Shiraz University, Shiraz, Iran

    Farhad Zare

  3. Department of Mechanical Engineering, California Baptist University, Riverside, CA, USA

    Xiuhua April Si

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  1. Amr Seifelnasr
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  2. Farhad Zare
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  3. Xiuhua April Si
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Amr Seifelnasr, Farhad Zare, Xiuhua April Si, and Jinxiang Xi. The first draft of the manuscript was written by Amr Seifelnasr, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Jinxiang Xi.

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Authors AS FZ and XSA declare they have no financial interests. Author JX has received research funding from AmPhastar Pharmaceuticals Inc. and MedSpray Inc.

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Seifelnasr, A., Zare, F., Si, X.A. et al. Optimized gravity-driven intranasal drop administration delivers significant doses to the ostiomeatal complex and maxillary sinus. Drug Deliv. and Transl. Res. (2023). https://doi.org/10.1007/s13346-023-01488-4

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