Modeling of release position and ventilation effects on olfactory aerosol drug delivery

Direct nose-to-brain drug delivery has multiple advantages over conventional intravenous deliveries. However, demonstration of its clinical feasibility is still in adolescence due to the lack of devices that effectively deliver medications to olfactory epitheliums. The objective of this study is to numerically evaluate two olfactory delivery protocols in a MRI-based nasal airway model: (1) pointed drug release in the vestibule (i.e., vestibular intubation), and (2) deep intubation with mediation released close to the olfactory mucosa. Influences of breathing maneuvers on olfactory delivery were also studied. It was observed that the front vestibular release gave higher olfactory dosage than the posterior vestibular release, and deep intubations yielded better outcomes than vestibular intubations. Specifically, the optimal olfactory dosage was achieved with deep intubation during inhalation. Breath-holding or exhalation, which was initially considered advantageous, resulted in unfocused depositions throughout the nasal turbinate region. Results of this study have implications for developing new olfactory delivery devices and for optimizing delivery protocols specific to patients' ventilations.

► Significantly improved olfactory dosages were achieved with proposed protocols. ► Drug release at front vestibule gives twice olfactory dosage than at back. ► Deep intubation with inhalation yields optimal olfactory depositions. ► Current delivery efficiencies are still too low to be clinically practical.