Links between the nose and the limbic system makes intranasal delivery a potential route for drugs to reach the central nervous system (CNS). However, so far most research has used rats, which have very different noses to humans, and doubts remain over delivering macromolecules.
These concerns were addressed by researchers at an AAPS Sunrise Session, entitled “Nose to Brain Delivery: Reality or Just Blowing Smoke?” Speaking at the session, Lisbeth Illum, CEO of Critical Pharmaceuticals, outlined the known nose-to-brain routes and barriers to adoption.
Illum said the three main challenges are: efficiently targeting the olfactory region, which is one of the three routes from nose-to-brain, the others being systemic and via the trigeminal nerve; retaining formulations in the olfactory region; and enhancing adsorption.
To efficiently target the olfactory region Illum believes novel nasal drug delivery devices will be needed. Another speaker at the session, Per Djupesland, chief scientific officer at OptiNose, gave a presentation on a device which is being developed to meet this need.
Djupesland said the human nose, and in particular the nasal valve, makes it difficult to deliver a therapeutic to the critical sites. To address these issues OptiNose has developed a breath actuated delivery device which it claims can target the olfactory region without lung deposition.
Studies suggest the device is capable of nose-to-brain delivery, said Djupesland, but it is much harder to validate this in humans than rats, largely because rats can be sacrificed to view the brain.
Macromolecules
In the other presentation Shyeilla Dhuria, a senior scientist at Novartis, showed research that delivered growth differentiation factor 5 (GDF-5), a molecule with a high molecular weight, to the mid-brain in rats.
Delivery to the mid-brain was achieved using a lipid nanosphere (LNS) formulation of GDF-5. Dhuria said use of LNS increased delivery to the mid-brain and other formulations could be used to target different pathways.
This would allow researchers to target different areas of the brain. For instance, the olfactory route of delivery is believed to reach the front of the brain, whereas the trigeminal nerve primarily administers drugs to the back of the brain.
Since CNS diseases often affect specific regions of the brain, for instance Pick’s disease often begins in the frontal lobe, the ability to target these regions could increase efficacy while decreasing side effects.
In light of this and other research Dhuria believes nose-to-brain delivery can become a reality. However, for it to succeed potent drugs with high solubility need to be found.