Visualization and Estimation of Nasal Spray Delivery to Olfactory Mucosa in an Image-Based Transparent Nasal Model

Abstract

Background: Nose-to-brain (N2B) drug delivery offers unique advantages over intravenous methods; however, the delivery efficiency to the olfactory region using conventional nasal devices and protocols is low. This study proposes a new strategy to effectively deliver high doses to the olfactory region while minimizing dose variability and drug losses in other regions of the nasal cavity. Materials and Methods: The effects of delivery variables on the dosimetry of nasal sprays were systematically evaluated in a 3D-printed anatomical model that was generated from a magnetic resonance image of the nasal airway. The nasal model comprised four parts for regional dose quantification. A transparent nasal cast and fluorescent imaging were used for visualization, enabling detailed examination of the transient liquid film translocation, real-time feedback on input effect, and prompt adjustment to delivery variables, which included the head position, nozzle angle, applied dose, inhalation flow, and solution viscosity. Results: The results showed that the conventional vertex-to-floor head position was not optimal for olfactory delivery. Instead, a head position tilting 45–60° backward from the supine position gave a higher olfactory deposition and lower variability. A two-dose application (250 mg) was necessary to mobilize the liquid film that often accumulated in the front nose following the first dose administration. The presence of an inhalation flow reduced the olfactory deposition and redistributed the sprays to the middle meatus. The recommended olfactory delivery variables include a head position ranging 45–60°, a nozzle angle ranging 5–10°, two doses, and no inhalation flow. With these variables, an olfactory deposition fraction of 22.7 ± 3.7% was achieved in this study, with insignificant discrepancies in olfactory delivery between the right and left nasal passages. Conclusions: It is feasible to deliver clinically significant doses of nasal sprays to the olfactory region by leveraging an optimized combination of delivery variables.

Intranasal Delivery of Anti-Apoptotic siRNA Complexed with Fas-Signaling Blocking Peptides Attenuates Cellular Apoptosis in Brain Ischemia

“…These anatomical distinctions pose difficulties in accurately determining effective intranasal drug dosing for human application, especially with experimental therapeutics like FBP9R/siRNA. However, recent technical advancements such as mucosal flap reconstruction and pressurized olfactory devices show promise in enhancing drug deposition beyond the nasal valve [ 69 , 70 ]. Continued exploration of such techniques may enhance the precision and clinical success of intranasal delivery for brain-associated disorders.…”

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

“…The nasal model N0, representing a normal condition, was previously developed from MRI scans of a 53-year-old male with no reported respiratory diseases [ 43 , 44 ]. The remaining three models (N1, P1, and P2) were modified from model N0, with changes made to the left inferior turbinate to reflect various degrees of congestion and decongestion.…”

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

“…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.…”

“…The effectiveness of nasal spray pumps in targeting specific areas within the nasal cavity is critically dependent on the intricacies of nasal cavity anatomy and functionality. These regions offer unique advantages for both targeted and systemic drug administration, which are influenced by factors including the drug formulation, the nasal spray pump design, the application method, and the deposition site, alongside the patient's nasal health [12][13][14][15]. However, conventional nasal sprays often fail to deliver drugs effectively to the posterior turbinate region and nasopharynx due to the geometrical complexity of the nasal cavity.…”

“…Effectively targeting the middle meatus, for instance, is recognized as a crucial strategy for the management of nasal polyposis and chronic rhinosinusitis [13,25,26]. The inconsistency introduced by nozzle retraction during the application process could undermine the delivery efficacy of protocols designed for conventional nasal spray pumps, which aim to deliver clinically significant medication doses to essential areas within the nasal cavity [14,27,28].…”