Nasal drug administration: potential for targeted central nervous system delivery

Nasal administration as a means of delivering therapeutic agents preferentially to the brain has gained significant recent interest. While some substrates appear to be delivered directly to the brain via this route, the mechanisms governing overall brain uptake and exposure remain unclear. Some substrates utilize the olfactory nerve tract and gain direct access to the brain, thus bypassing the blood-brain barrier (BBB). However, most agents of pharmacologic interest likely gain access to the brain via the olfactory epithelium, which represents a more direct route of uptake. While the traditional BBB is not present at the interface between nasal epithelium and brain, P-glycoprotein (and potentially other barrier transporters) is expressed at this interface. In addition, work in this laboratory has demonstrated that P-glycoprotein throughout the brain can be modulated with nasal administration of appropriate inhibitors. The potential for targeted central nervous system delivery via this route is discussed.