[Frontiers in Bioscience S4, 74-89, January 1, 2012]

Intranasal treatment of neurodegenerative diseases and stroke

Diana Gomez1, Jose A. Martinez1, Leah R. Hanson2, William H. Frey II2, Cory C. Toth2

1Department of Clinical Neurosciences and The Hotchkiss Brain Institute, The University of Calgary, Calgary, AB, Canada, 2Alzheimer's Research Center at Regions Hospital, HealthPartners Research Foundation, St. Paul, Minnesota 55101

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Pathways and mechanisms of intranasal delivery
3.1. Olfactory nerve pathways
3.2. Trigeminal nerve pathways
3.3. Vascular pathways
3.4. Pathways involving the cerebrospinal fluid and lymphatics
4. Delivery and formulation considerations in intranasal delivery
5. Limitations of intranasal delivery
6. Application of intranasal delivery techniques to neurodegenerative processes
6.1. Alzheimer's disease and dementia
6.2. Diabetes and the neurodegenerative brain
7. Application of intranasal delivery to the treatment of stroke
8. The future of intranasal delivery
9. Conclusion
10. References

1. ABSTRACT

Although the blood-brain barrier (BBB) restricts access to the central nervous system (CNS) for the use of systemically administered therapies, an alternative approach, the non-invasive method of intranasal delivery, can rapidly target delivery of molecules to the CNS. Intranasal delivery has the distinct advantages of circumventing the BBB while minimizing systemic exposure. This novel approach to treating neurological illnesses will be examined in detail in this review. We will review current understanding of the mechanisms underlying intranasal delivery to the CNS, along with discussion of pathways permitting entry from the nasal cavity into the CNS, particularly those involving the olfactory and trigeminal nerves. Significant preclinical research has been performed to develop and improve our current approaches to intranasal treatments. We will examine the evidence behind the use of intranasal delivery in chronic neurodegenerative conditions such as Alzheimer's Disease and diabetes-mediated cerebral degeneration, as well as in acute conditions such as stroke.