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Nasal Cycling Effects in Intranasal Drug Delivery Efficiency to the Olfactory Cleft.

Michelle H Kim,Dennis O Frank-Ito

Published 2025 in Respiratory Physiology & Neurobiology

ABSTRACT

BACKGROUND Optimizing olfactory cleft drug delivery remains a significant challenge due to the anatomical complexity of the nasal cavity and olfactory cleft location. While various strategies have been explored to improve targeting, the influence of nasal cycling remains poorly understood. This study investigates the impact of nasal cycling on olfactory-targeted drug delivery. METHODS Three-dimensional nasal airway models were reconstructed from radiographic images of 32 healthy adults and classified into Mid (n=16), Mild (n=8), and Extreme (n=8) nasal cycling. Computational simulations were conducted at 15L/min inspiratory flowrate. Drug particle transport was simulated under varied conditions, including spray velocities (1, 5, 10m/s), plume angles (10°, 20°, 40°, 70°), and release locations (10mm Center, 20mm Center, 20mm Mid-Superior, and 20mm Max-Superior) with head held upright. 175,000 drug particles (1-50μm) were released per nostril. RESULTS Across all classifications, olfactory deposition was greater on less patent (LP) side (median: Mid=4.89%, Mild=1.82%, Extreme=5.32%) than more patent (MP) side (median: Mid=1.31%, Mild=0.25%, Extreme=0.23%). Pairwise comparisons revealed no statistically significant differences in deposition between cycling classifications for either LP or MP (all p>0.05), with effect sizes indicating small differences (rank-biserial correlation range: LP=-0.19-0.06; MP=0.02-0.26). Narrow plume angles (10°) consistently enhanced LP deposition, wider angles (70°) were more effective on MP. Spray release location varied according to cycling classification, and 1m/s spray velocity yielded the highest frequency of olfactory deposition across all cycling states. CONCLUSION These preliminary results demonstrate that nasal cycling exerts a dynamic influence on intranasal drug deposition patterns within the olfactory cleft.

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