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. 2022 Jun 8;10(6):1347.
doi: 10.3390/biomedicines10061347.

Olfactory Drug Aerosol Delivery with Acoustic Radiation

Mohammad Yaghoub Abdollahzadeh Jamalabadi  1 , Jinxiang Xi  1
Affiliations

Olfactory Drug Aerosol Delivery with Acoustic Radiation

Mohammad Yaghoub Abdollahzadeh Jamalabadi et al. Biomedicines. .

Abstract

Nose-to-brain (N2B) drug delivery is a new approach to neurological disorder therapy as medications can bypass the blood-brain barrier and directly enter the brain. However, the delivery efficiency to the olfactory region using the conventional delivery method is impractically low because of the region's secluded position in a convoluted nasal cavity. In this study, the acoustic radiation force was explored as an N2B delivery alternative in a wide frequency range of 10-100,000 Hz at an increment of 50 Hz. Numerical simulations of the particle deposition in the olfactory region of four nasal configurations were performed using COMSOL. Frequency analysis of the nasal cavities revealed that eigenfrequencies were often associated with a specific region with narrow passages and some eigenfrequencies exhibited an amendable pressure field to the olfactory region. Transient particle tracking was conducted with an acoustic inlet at 1 Pa, and a frequency spectrum of 10-100,000 Hz was imposed on the airflow, which carried the particles with acoustic radiation forces. It was observed that by increasing the pulsating wave frequency at the nostrils, the olfactory delivery efficiency reached a maximum in the range 11-15 kHz and decreased after that. The correlation of the olfactory delivery efficiency and instantaneous values of other parameters such as acoustic velocity and pressure in the frequency domain was examined.

Keywords: acoustic radiation; active particle control; direct nose-to-brain delivery; olfactory deposition.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Prevalence and treatment of neurological disorders (NDs): (a) various types of NDs and their prevalence (scale: the green circle representing 3 million patients), and (b) four stages of nose-to-brain (N2B) drug delivery: (1) intranasal drug delivery to the olfactory mucosa, (2) drug transport from the olfactory mucosa to the brain (tissue transport), (3) drug action in the brain (pharmacodynamics), and (4) drug elimination from the brain and body.
Figure 2
Figure 2
Computational models: (a) nose model geometry consisting of the nostril, vestibule, nasal valve, turbinate, nasopharynx, and the olfactory region, (b) four models with varying obstructions: Cases 1–4 with a progressively shrunk inferior turbinate, (c) cross-sections of Cases 1–4.
Figure 3
Figure 3
Eigenfrequency analysis.
Figure 4
Figure 4
Predicted olfactory deposition at varying frequencies.
Figure 5
Figure 5
Comparison between obtained results of frequency analysis of (a) Case 1, (b) Case 2, (c) Case 3, (d) Case 4, and (e) all cases with an average line.
Figure 6
Figure 6
Effect of Brownian motion on olfactory deposition in the baseline case (Case 2).
Figure 7
Figure 7
Comparison of acoustic pressure at some point at the top of olfactory volume and bottom of that region within the frequency range of (a) 5–6 kHz, and (b) 14,250 to 14,750 Hz.
Figure 8
Figure 8
Comparison of acoustic pressure isosurfaces among four nasal geometries: (a) low-frequency range (5–6 kHz), and (b) high-frequency range (14.25–14.75 kHz).
Figure 9
Figure 9
Comparison of particle surface deposition distribution among four nasal geometries: (a) low-frequency range (5–6 kHz), and (b) high-frequency range (14.25–14.75 kHz).
Figure 10
Figure 10
A general correlation between (a) acceleration in the y-direction, (b) acoustic pressure, and the olfactory deposition.
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