Abstract

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.

Graphical Abstract