The nasal olfactory region is a potential route for non-invasive
delivery of drugs directly from the nasal epithelium to the brain,
bypassing the often impermeable blood-brain barrier. However, efficient
aerosol delivery to the olfactory region is challenging due to its
location in the nose. Here we explore aerosol delivery with
bi-directional pulsatile flow conditions for targeted drug delivery to
the olfactory region using a computational fluid dynamics (CFD) model on
the patient-specific nasal geometry. Aerosols with aerodynamic diameter
of 1 µm, which is large enough for delivery of large enough drug doses
and yet potentially small enough for non-inertial aerosol deposition due
to, e.g., particle diffusion and flow oscillations, is inhaled for
1.98 s through one nostril and exhaled through the other one. The
bi-directional aerosol delivery with steady flow rate of 4 L/min results
in deposition efficiencies (DEs) of 50.9 and 0.48% in the nasal cavity
and olfactory region, respectively. Pulsatile flow with average flow
rate of 4 L/min (frequency: 45 Hz) reduces these values to 34.4 and
0.12%, respectively, and it mitigates the non-uniformity of right-left
deposition in both the cavity (from 1.77- to 1.33-fold) and the
olfactory region (from 624- to 53.2-fold). The average drug dose
deposited in the nasal cavity and the olfactory epithelium region is
very similar in the right nasal cavity independent of pulsation
conditions (inhalation side). In contrast, the local aerosol dose in the
olfactory region of the left side is at least 100-fold lower than that
in the nasal cavity independent of pulsation condition. Hence, while
pulsatile flow reduces the right-left (inhalation-exhalation) imbalance,
it is not able to overcome it. However, the inhalation side (even with
pulsation) allows for relatively high olfactory epithelium drug doses
per area reaching the same level as in the total nasal cavity. Due to
the relatively low drug deposition in olfactory region on the exhalation
side, this allows either very efficient targeting of the inhalation
side, or uniform drug delivery by performing bidirectional flow first
from the one and then from the other side of the nose
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