Sniffing Your Way to Brain Treatment: How Nasal Sprays Could Deliver Peptide Drugs Directly to the Brain

Nose-to-brain (N-to-B) delivery offers a non-invasive way to get peptide drugs into the brain by bypassing the blood-brain barrier entirely. The olfactory and trigeminal nerves provide direct pathways from the nasal cavity to the brain, allowing peptide drugs to reach the CNS without needing injections or having to survive the digestive system. This approach can rapidly target the brain while minimizing systemic exposure and side effects. The review covers clinical applications, nasal delivery devices, and the current limitations of this approach.

Narrative review of published literature on intranasal peptide delivery, covering the anatomy and physiology of nose-to-brain transport, formulation strategies, clinical applications across CNS diseases, nasal delivery devices, and the limitations and challenges of the approach.

The blood-brain barrier blocks over 98% of potential drugs from reaching the brain, making brain diseases among the hardest to treat. Peptides are particularly promising for neurological conditions due to their specificity and low toxicity, but they can't cross the BBB or survive oral delivery. Nose-to-brain delivery solves both problems at once — getting peptides to the brain without surgery, injections, or the digestive tract. This could transform treatment for Alzheimer's, Parkinson's, depression, chronic pain, and brain tumors.

Nose-to-brain delivery has gained significant momentum as peptide therapeutics for neurological diseases have expanded. Intranasal insulin for Alzheimer's and intranasal oxytocin for social disorders have already reached clinical trials. As the peptide drug pipeline grows — including neuroprotective peptides, neurotrophic factors, and pain-modulating peptides — the N-to-B delivery route could become the standard way to get these molecules to where they're needed. The approach also aligns with patient preference for non-invasive treatments over injections.

The review is broad and does not present original data. While the concept of nose-to-brain delivery is well-established, many applications are still in early research stages. Challenges include variable absorption depending on nasal anatomy and health, limited dose volumes, mucociliary clearance that removes drugs, and difficulty controlling dosing precision. Translation from animal models (especially rodents, which have proportionally larger olfactory regions) to humans has been inconsistent.