The nasal approach to delivering treatment for brain diseases: an anatomic, physiologic, and delivery technology overview

Djupesland PG, Messina JC, Mahmoud RA. The nasal approach to delivering treatment for brain diseases: anatomic, physiologic and delivery technology overview. Therapeutic Delivery. 2014 5(6), 709–733.



The intricate pathophysiology of brain disorders, difficult access to the brain, and the complexity and high risks and costs of drug development represent major hurdles for improving therapies. Nose-to-brain drug transport offers an attractive alternative or addition to formulation-only strategies attempting to enhance drug penetration into the CNS. Although still a matter of controversy, many studies in animals claim direct nose-to-brain transport along the olfactory and trigeminal nerves, circumventing the traditional barriers to CNS entry. Some clinical trials in man also suggest nose-to-brain drug delivery, although definitive proof in man is lacking. This review focuses on new nasal delivery technologies designed to overcome inherent anatomical and physiological challenges and facilitate more efficient and targeted drug delivery for CNS disorders.


N2B transport is a promising emerging field that may be one of the solutions for the significant difficulties in getting emerging brain therapies into the CNS where they can achieve the desired activity. The barriers to CNS entry of drugs include both the BBB and the BCSFB, and these challenge research into N2B transport. The evidence for N2B transport that has already been developed in animals and the mechanisms for such transport and the issues that surround translating animal research into human implications have been discussed. We have reviewed core concepts in human nasal anatomy and physiology, how they influence nasal drug deposition patterns and the potential for achieving N2B drug transport in man. We have also discussed the limitations of in vitro models and CFD simulations and the important need for human studies of drug deposition. Lastly, we have provided a scan of available technologies for delivering drugs in a manner that may produce N2B transport and a review of the available data to suggest successful N2B type deposition and transport.