Intranasal delivery of neuropeptides.

A major barrier to entry of neuropeptides into the brain is low bioavailability and presence of the blood-brain barrier. Intranasal delivery of neuropeptides provides a potentially promising alternative to other routes of administration, since a direct pathway exists between the olfactory neuroepithelium and the brain. Use of the rat as an animal model in nose to brain delivery of neuropeptides allows for several advantages, including a large surface area within the nasal cavity dedicated to olfactory epithelium and robust neuronal pathways extending to and from most areas of the brain from the nose via the olfactory cortex. A major disadvantage to using rats for nose to brain delivery is the difficulty in selectively targeting the posterior olfactory epithelium (which facilitates delivery to the brain) over the more anterior respiratory epithelium (which facilitates delivery to the lungs and secondarily to the peripheral blood) in the nasal cavity. We have developed a novel delivery system that consists of surgically implanting stainless-steel cannulas in the dorsal aspect of the nasal cavity overlying the olfactory neuroepithelium, thereby allowing neuropeptide compounds to bypass the respiratory epithelium.