Assessing Nasal Epithelial Dynamics: Impact of the Natural Nasal Cycle on Intranasal Spray Deposition

Abstract

This study investigated the intricate dynamics of intranasal spray deposition within nasal models, considering variations in head orientation and stages of the nasal cycle. Employing controlled delivery conditions, we compared the deposition patterns of saline nasal sprays in models representing congestion (N1), normal (N0), and decongestion (P1, P2) during one nasal cycle. The results highlighted the impact of the nasal cycle on spray distribution, with congestion leading to confined deposition and decongestion allowing for broader dispersion of spray droplets and increased sedimentation towards the posterior turbinate. In particular, the progressive nasal dilation from N1 to P2 decreased the spray deposition in the middle turbinate. The head angle, in conjunction with the nasal cycle, significantly influenced the nasal spray deposition distribution, affecting targeted drug delivery within the nasal cavity. Despite controlled parameters, a notable variance in deposition was observed, emphasizing the complex interplay of gravity, flow shear, nasal cycle, and nasal morphology. The magnitude of variance increased as the head tilt angle increased backward from upright to 22.5° to 45° due to increasing gravity and liquid film destabilization, especially under decongestion conditions (P1, P2). This study’s findings underscore the importance of considering both natural physiological variations and head orientation in optimizing intranasal drug delivery.

Effects of Nozzle Retraction Elimination on Spray Distribution in Middle-Posterior Turbinate Regions: A Comparative Study

“…The MOD device was adapted from a conventional multi-dose nasal spray pump by detaching the nozzle from the actuator and connecting it to the dispensing mechanism with a flexible plastic tube, thereby eliminating nozzle retraction during application. The experimental setup utilized two multi-piece, transparent, and anatomically accurate models of the left nasal passage of a healthy adult male (Figure 1a-c), which were previously used in a study assessing the natural nasal cycle's effect on intranasal spray deposition [24]. These models, named N1 (negative 1) and P1 (positive 1) in the previous study [24] and renamed model 1 (M1) and model 2 (M2) in this study, feature distinct turbinate geometries to represent variations in nasal passage morphologies.…”

“…The experimental setup utilized two multi-piece, transparent, and anatomically accurate models of the left nasal passage of a healthy adult male (Figure 1a-c), which were previously used in a study assessing the natural nasal cycle's effect on intranasal spray deposition [24]. These models, named N1 (negative 1) and P1 (positive 1) in the previous study [24] and renamed model 1 (M1) and model 2 (M2) in this study, feature distinct turbinate geometries to represent variations in nasal passage morphologies. Each cast consisted of five sections-front, turbinate 1 (T1), turbinate 2 (T2), turbinate 3 (T3), and nasopharynx (NP)-with step-shaped grooves at the interface for tight seal (Figure 1).…”

“…The nasal models, M1 and M2 (Figure 1), were developed from MRI scans of a 53-yearold male [14,24]. Both models were created based on the left nasal passage, including the nasal septum, to allow for clear visualization of spray delivery, liquid film mobilization, and final deposition distribution within the turbulent region during the experimental runs.…”

“…Moreover, the success of medications administered through nasal spray pumps heavily relies on inspiratory flow. This flow is vital for moving the medication efficiently through the nasal pathways to the desired regions, ensuring effective drug delivery for optimal absorption or therapeutic impact [24]. The variability in individual nasal structures also plays an important role, markedly affecting medication distribution within the nasal passages and, consequently, the overall success of the intranasal delivery system [13].…”