Figure 1.

The human nose-to-brain anatomy. In humans, the nasal cavity contains three major regions based on epithelial type. The first most anterior vestibule (dark yellow), is comprised of squamous epithelial cells and does not play a significant role in drug absorption/uptake. Just posterior to the anterior vestibule is the respiratory epithelium (yellow). Drugs (green arrows) absorbed across the respiratory epithelium can be deposited into the lamina propria where they gain access to an extensive pathway to the brain along the branches of the trigeminal nerve. Drugs can travel intraneuronally or in a perineural and perivascular distribution to enter the brain via the trigeminal ganglion (red) and brainstem (red). Finally, posteriorly and dorsally lies the olfactory epithelium (bright yellow), which houses the olfactory neurons (blue), and is situated at the posterior and dorsal aspect of the nasal cavity. These neurons send cilia into the nasal cavity lumen. Drugs can be absorbed into the olfactory receptors or traverse the olfactory epithelium to gain access to the olfactory bulb by transcellular or perineuronal/perivascular routes within the lamina propria. From the olfactory bulb (blue), drugs (purple arrows) gain access to the brain (pink).