In Silico Study to Enhance Delivery Efficiency of Charged Nanoscale Nasal Spray Aerosols to the Olfactory Region...

Various factors and challenges are involved in efficiently delivering drugs using nasal sprays to the olfactory region to treat central nervous system diseases. In this study, computational fluid dynamics was used to simulate nasal drug delivery to (1) examine effects on drug deposition when various external magnetic fields are applied to charged particles, (2) comprehensively study effects of multiple parameters (i.e., particle aerodynamic diameter; injection velocity magnitude, angle, and position; magnetic force strength and direction), and (3) determine how to achieve the optimal delivery efficiency to the olfactory epithelium. The Reynolds-averaged Navier-Stokes equations governed airflow, with a realistic inhalation waveform implemented at the nostrils. Particle trajectories were modeled using the one-way coupled Euler-Lagrange model. A current-carrying wire generated a magnetic field to apply force on charged particles and direct them to the olfactory region. Once drug particles reached the olfactory region, their diffusion through mucus to the epithelium was calculated analytically. Particle aerodynamic diameter, injection position, and magnetic field strength were found to be interconnected in their effects on delivery efficiency. Specific combinations of these parameters achieved over 65-fold higher drug delivery efficiency compared with uniform injections with no magnetic fields. The insight gained suggests how to integrate these factors to achieve the optimal efficiency.