Nasal Physiology and Drug Transport

Once a compound enters the nasal cavity, it can be navigated along several pathways. There is a chance for a drug to be: (1) rapidly cleared by the mucociliary mechanism, (2) absorbed and reach the systemic circulation (lipophilic compounds mostly), and (3) absorbed by the olfactory epithelium and reach the olfactory bulb. When a drug compound is cleared away in the nasal cavity, it is degraded by enzymes in the nasal mucus, which therefore interrupts the drug delivery to the target zone. A drug compound can also enter the systemic circulation and may effectively reach the target area followed by elimination from the blood by clearance mechanisms present throughout the body. In case of the latter, to reach the brain the drug has to bypass the BBB, which is an obstacle for most hydrophilic and/or large compounds. Moreover, once the compound passes through the BBB into the brain it can still be eliminated from the CSF back into the blood circulation. Furthermore, a drug compound entering the nasal cavity can also pass through the olfactory epithelium and reach the olfactory bulb, which can transport the drug into the brain without facing the BBB.