THE LANCET Neurology Vol 1 July 2002
Could a transnasal route be used for drug delivery to the brain? Jan Born (University of Lübeck, Germany) and colleagues report that intranasal administration of three neuropeptides —melanocortin(4–10), vasopressin, and insulin—to 36 healthy people resulted in accumulation of each peptide in the CSF within 30 min. Except for vasopressin, the researchers saw no increase in blood concentrations of the peptides over the same time period (Nat Neurosci 2002; 5: 514–6). William Frey (University of Minnesota, Minneapolis, MN, USA) notes that this research builds on results previously obtained in animal models and “provides more evidence that intranasal delivery may fundamentally alter the way we treat diseases and disorders of the CNS”.
The more we learn about neuropeptides and how they function in the brain, the more likely it seems that some of them could be valuable therapeutic agents. However, delivery of neuropeptides, and indeed other therapeutic agents, to the brain is problematic because of the blood-brain barrier (BBB). Intracerebroventricular injection of drugs is one way to circumvent the BBB, but says Born, “for ethical reasons, this invasive technique can only be used in severely ill patients”.
Intranasal delivery is a potential, non-invasive way to bypass the BBB. It has been known for years that some small molecules can pass directly from the submucous space of the nose to the CSF of the olfactory lobe and then circulate within the CSF flow tracts of the brain. Born’s current work seems to extend this administration route to neuropeptides. “But, transnasal delivery does not deliver a drug deep into the brain parenchyma”, cautions William Pardridge (University of California, Los Angeles, CA, USA). “The drug is only delivered to the CSF and will be cleared back into the peripheral blood before there is time for it to be carried to brain tissue.”
Born agrees that he has not directly demonstrated neuropeptide delivery to brain parenchyma in human beings, “but the results of animal studies indicate that nasally delivered peptides reach the more interior structures of the brain. We are now looking into the possibility of using imaging methods such as magnetic resonance spectroscopy to monitor neuropeptide delivery to brain structures in people.”