Neurological drugs delivered to the olfactory region can enter the brain via olfactory pathways
and bypass the blood-brain barrier. However, clinical applications of the direct nose-to-brain delivery
are rare because of the extremely low olfactory doses using conventional nasal devices. This
poor bioavailability is mainly caused by two factors: the complex nasal structure that traps particles in
the anterior nose and the complete lack of control over particle motions after their release at the nostrils.
In this study, the feasibility of electric-guided delivery to the olfactory region was tested in an anatomically accurate
nasal airway model both experimentally and numerically. The nose replicas were prepared using 3-D printing and could
be dissembled to reveal the local deposition patterns within the nasal cavity. A test platform was developed that included a
dry powder charging system and a particle point-release nozzle. Numerical modeling was conducted using COMSOL and
compared to corresponding experiments. Compared to conventional nasal devices, electric-guidance of charged particles
noticeably reduced particle losses in the anterior nose and increased depositions in the olfactory region. The thickness and
relative permittivity of the wall were observed to affect the electric field strength and olfactory dosages. Consistent deposition
patterns were obtained between experiments and numerical simulations in both 2-D and 3-D nose models. Two conceptual
designs were proposed to generate, charge, and control aerosols. Results of this study indicate that it is feasible to
use an electric field to control charged particles in the human nose. Both electric-guidance and point-release of particles
are essential to achieve targeted olfactory delivery. Future studies to refine the aerosol charging and release systems are
needed for further enhancement of olfactory dosages.
Keywords: Olfactory region, electric-guidance, charged particles, intranasal aerosol drug delivery, point-release, direct noseto-
brain drug delivery.
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