Numerical analysis of enhanced nano-drug delivery to the olfactory bulb

Central Nervous System (CNS) disorders are one of the major causes of fatalities in the world today. Thus, it is essential to transport a considerable amount of drugs to a specific brain location for any treatment to be effective. A noninvasive approach is direct nanodrug delivery via the nasal route. The main pathway for these drugs into the brain requires crossing the Blood-Brain Barrier (BBB), located along the olfactory region of the nasal cavity. Tight junctions of the BBB allow only nanoparticles of sufficiently high concentrations to pass through. Multifunctional nanoparticles can be used to target the brain via the olfactory bulb. Computational Fluid-Particle Dynamics (CF-PD) simulations offer a manageable, accurate and cost-effective route for studying this possibility. For the present study, the open-source CFD toolbox OpenFOAM was employed to conduct all fluid-particle dynamics simulations. Previous studies have shown that normal injection of particles through the nostrils have shown clinically insignificant amounts of olfactory deposition. The main objective of this study is to utilize the Particle Release Map (PRM) methodology to optimize the nanodrug deposition efficiency inside the olfactory region, using a representative human nasal cavity as a test bed. While published results indicate maximum olfactory depositions of 3 to 4% (for 1 nm particles) under normal breathing rate, the PRM approach achieves 28.4% deposition for 10 nm and 8.7% for 100 nm particles in the olfactory bulb. Practically, such elevated olfactory depositions with the PRM technique could be achieved in conjunction with a well-placed nasal cannula. Copyright (c) 2021 American Association for Aerosol Research