Nasal spray delivery can transport therapeutic peptides directly to the brain via the olfactory and trigeminal nerves, bypassing the blood-brain barrier without injections.
Bypasses the BBBThe olfactory and trigeminal nerves provide direct pathways from the nose to the brain, allowing peptide drugs to reach the CNS without crossing the blood-brain barrier
What the researchers found
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.
Why it matters
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.
The numbers in context
Routes: olfactory nerve + trigeminal nerve pathways · Bypasses BBB · Minimizes systemic exposure · Non-invasive alternative to injection · Applications: psychiatric disorders, neurodegeneration, pain, stroke, brain tumors
How the study worked
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.
Who was studied
Review covering preclinical and clinical research on intranasal peptide delivery for CNS disorders
What this study cannot tell us
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.
How to read the evidence
This is a narrative review published in Pharmaceutics, covering both established principles and emerging applications of nose-to-brain peptide delivery. It synthesizes a broad literature but is a secondary source without original experimental data.
When this study was published
Published in 2022, this review captures a period of active development in intranasal drug delivery technology. Several clinical trials for intranasal peptides have been initiated or completed since its publication.
The bigger picture
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.
Questions still open
- How much of a nasal peptide dose actually reaches the brain versus being absorbed systemically or cleared by mucus?
- Can nasal delivery devices be optimized to target the olfactory region specifically for maximum brain transport?
- Will nose-to-brain delivery scale from research peptides to blockbuster neurological drugs?
Common questions
How do nasal sprays get drugs into the brain?
What brain diseases could be treated with nasal peptide sprays?
Read the original research
Nose-to-Brain Delivery of Therapeutic Peptides as Nasal Aerosols.
Pharmaceutics, 14(9)
Citation
Alabsi, Wafaa; Eedara, Basanth Babu; Encinas-Basurto, David; Polt, Robin; Mansour, Heidi M. (2022). Nose-to-Brain Delivery of Therapeutic Peptides as Nasal Aerosols.. Pharmaceutics, 14(9). https://doi.org/10.3390/pharmaceutics14091870