Intranasal peptide delivery: what the research literature actually shows

Why researchers look at the nasal route

Taken by mouth, unmodified peptides are broken down by digestive proteases and absorbed poorly, so their oral bioavailability is usually very low. Injection avoids that problem, which makes alternatives to injection an active area of formulation science.

The nasal cavity has a thin, well-supplied lining and bypasses the gut and the liver's first pass, so it has long been investigated as a route for small peptides and, in some cases, for reaching the brain.

The barriers inside the nose

The nasal lining is not a free pass. Several features limit how much of a peptide is absorbed:

• Mucociliary clearance: the mucus layer is swept toward the throat within minutes, limiting contact time.
• Tight junctions between cells restrict the passage of larger or charged molecules.
• Local peptidases in the mucosa can degrade a peptide before it is absorbed.
• Size: absorption generally falls as molecular mass rises, which favours short peptides.

Nose-to-brain transport

The olfactory and trigeminal nerves provide a direct anatomical connection between the nasal cavity and the brain. Animal and human studies show that some material can travel along these pathways.

The important caveat is proportion. Studies of how liquid is distributed in the nose indicate that only a small share of a sprayed volume reaches the olfactory region, and the share that enters the brain is smaller still. Any claim that a spray delivers a peptide to the brain efficiently should be treated as unproven.

Formulation adds variability

A nasal product is a formulation, not just a molecule. The chemical stability of a peptide in water, the pH and preservative system, the particle or droplet size produced by the device, and individual anatomy all change what is delivered.

Peptides are also less stable in solution than as a dry powder, which is why comparisons between a nasal solution and a lyophilised powder are not like-for-like. See the guide on handling lyophilised peptides for the stability basics.

What the evidence looks like for commonly discussed peptides

Semax and Selank are the peptides most often discussed in a nasal context. Much of the published human data on them comes from small studies in the Russian-language literature, with sample sizes in the tens, and they have not been reviewed or independently replicated by Western regulators.

Intranasal oxytocin and kisspeptin have been studied more widely in research settings, but findings vary between studies and are an active area of debate rather than settled fact.

How to read a nasal-spray claim

A product page that makes strong claims without answering these questions is describing marketing, not evidence.

• Does it cite human data, or only cell and animal work?
• Does it state how much reaches the bloodstream or the brain, and from what study?
• Is the regulatory status stated plainly? None of the research peptides discussed here is approved as a nasal medicine on the basis of this evidence.
• Is the formulation described, including what the peptide is dissolved in?