Parameter characteristics in intranasal drug delivery: A key to targeting medications to the olfactory airspace.

BACKGROUND: The nose is a viable pathway for topical drug delivery to the olfactory cleft for treatment of obstructive smell loss and nose-to-brain drug delivery. This study investigates how variations in nasal vestibule morphology influence intranasal spray drug transport to the olfactory cleft and olfactory roof/bulb regions.

METHODS: The unilateral nasal vestibule morphology in three healthy subjects with healthy normal nasal anatomy was classified as Elongated (Subject DN001), Notched (Subject DN002), and Standard (Subject DN003). Computational fluid and particle dynamics modelling were used to simulate nasal airflow and drug particle transport to the olfactory cleft and olfactory roof/bulb regions in each subject-specific nasal cavity. To evaluate highest drug depositions in these regions, the particle transport simulations involved extensive parameter combination analyses: 6 inspiratory flow rates mimicking resting to sniffing (10-50 L/min); 5 spray release locations (Top, Bottom, Central, Lateral, and Medial); 5 head positions (Upright, Tilted Forward, Tilted Back, Supine, and Mygind); 3 particle velocities (1, 5, and 10 m/s); 350,000 μm-particles (1-100 μm) and 346,500 nanoparticles (10-990 nm).

FINDINGS: Particle size groups with highest depositions in olfactory cleft: DN001 left = 28.4% at 11-20 μm, right = 75.3% at 6-10 μm; DN002 left = 16.8% at 1-5 μm, right = 45.3% at 30-40 nm; DN003 left = 29.1% at 21-30 μm, right = 15.9% at 6-10 μm. Highest depositions in olfactory roof/bulb: DN001 left = 6.5% at 11-20 μm, right = 26.4% at 11-20 μm; DN002 left = 3.6% at 1-5 μm, right = 2.6% at 1-5 μm; DN003 left = 2.8% at 21-30 μm, right = 1.7% at 31-40 μm.

INTERPRETATION: DN001 (Elongated nasal vestibule) had the most deposition in the olfactory regions. Micron-particles size groups generally had better deposition in the olfactory regions.