Peptide Nasal Sprays: How They Work and Which Peptides Use Them

The nasal cavity offers a surprisingly effective route for delivering certain peptides into the bloodstream and, in some cases, directly to the brain. The nasal mucosa — the moist lining of the nasal passages — is richly supplied with blood vessels and has a large surface area (approximately 150 cm² in adults), making it an efficient site for absorption.

When a peptide solution is sprayed into the nose, the molecules come into contact with the nasal epithelium, a thin layer of cells that separates the nasal cavity from the underlying capillary network. Small, lipophilic molecules can cross this barrier relatively easily through transcellular transport (passing through cells) or paracellular transport (passing between cells through tight junctions).

A particularly interesting feature of nasal delivery is the potential for nose-to-brain transport. The olfactory region at the top of the nasal cavity is in close proximity to the olfactory bulb and the central nervous system. Some peptides can travel along the olfactory and trigeminal nerve pathways, bypassing the blood-brain barrier entirely. This makes intranasal delivery especially attractive for neuropeptides intended to act on the brain.

It is worth noting that intranasal delivery is not suitable for all peptides. Molecular size, charge, stability in solution, and susceptibility to enzymatic degradation in the nasal cavity all influence whether a given peptide can be effectively delivered via this route.

One of the key considerations for any drug delivery route is bioavailability — the proportion of the administered dose that reaches the systemic circulation in an active form. For peptides, injectable routes (subcutaneous or intramuscular) generally provide the highest bioavailability, often approaching 90–100%.

Intranasal bioavailability for peptides is typically lower, ranging from approximately 5% to 50% depending on the specific compound, formulation, and whether absorption enhancers are used. Factors that reduce nasal bioavailability include mucociliary clearance (the continuous movement of mucus that sweeps particles toward the throat), enzymatic degradation by proteases in the nasal mucosa, and the molecular weight barrier — peptides larger than approximately 10 kDa are generally poorly absorbed nasally.

Despite the lower absolute bioavailability, nasal delivery offers compensating advantages. The rapid onset of action (often within 5–15 minutes) can be advantageous for peptides where timing matters, such as those affecting mood or cognition. The avoidance of first-pass hepatic metabolism means that nasally absorbed peptides reach their targets without being partially degraded by the liver, which can partially offset the lower overall absorption.

Modern nasal formulations increasingly incorporate absorption enhancers — excipients like cyclodextrins, chitosan, or phospholipids that temporarily increase the permeability of the nasal epithelium without causing lasting damage. These can significantly improve bioavailability for certain peptides, closing the gap with injectable administration.

Several peptides have been studied or are commercially available in intranasal formulations. Each leverages the unique properties of nasal delivery for specific therapeutic or research purposes.

Selank is a synthetic analogue of the naturally occurring immunomodulatory peptide tuftsin, with an additional sequence that enhances its stability. It has been studied for its anxiolytic and nootropic effects, and intranasal delivery allows it to reach the central nervous system via olfactory pathways. In Russia, Selank has been approved as a nasal spray formulation for anxiety disorders, though it remains a research compound in the UK and most other countries.

Semax is a synthetic analogue of ACTH(4-10) that has been studied for neuroprotective and cognitive-enhancing properties. Like Selank, it benefits from intranasal delivery due to its central nervous system targets. Research has investigated its use in stroke recovery, cognitive decline, and attention disorders.

Oxytocin is a well-characterised peptide hormone naturally produced in the hypothalamus. Intranasal oxytocin has been extensively studied for its effects on social behaviour, trust, empathy, and anxiety reduction. The nasal route is particularly advantageous for oxytocin because it provides access to brain regions involved in social cognition.

DSIP (Delta Sleep-Inducing Peptide) is a neuropeptide that has been studied for its role in sleep regulation and stress response. Intranasal delivery provides convenient dosing before bedtime without the need for injection.

PT-141 (bremelanotide) was originally studied as an intranasal formulation for sexual dysfunction before being reformulated as a subcutaneous injection (approved as Vyleesi in the United States). The switch from nasal to injectable was partly driven by concerns about blood pressure effects and variable absorption via the nasal route.

Intranasal peptide delivery offers several compelling advantages over injectable administration, but it is not without significant limitations.

Advantages: - Non-invasive and needle-free: Eliminates the discomfort, anxiety, and infection risk associated with injections, significantly improving compliance - Rapid absorption: Onset of effects typically occurs within 5–15 minutes, compared to 15–30 minutes for subcutaneous injection - Nose-to-brain pathway: Provides a potential route to bypass the blood-brain barrier for centrally acting peptides - Self-administration simplicity: Requires minimal training compared to injection technique, and can be performed discreetly - No first-pass metabolism: Avoids hepatic degradation that can reduce the bioavailability of orally administered peptides

Limitations: - Lower and more variable bioavailability: Absorption can be affected by nasal congestion, mucus production, and individual anatomical differences - Volume constraints: Each nostril can typically accommodate only 100–150 µL per spray, limiting the total dose per administration - Nasal irritation: Repeated use may cause dryness, irritation, or epistaxis (nosebleeds) in some individuals - Not suitable for all peptides: Larger peptides (>10 kDa) and those unstable in aqueous solution are poor candidates for nasal delivery - Enzymatic degradation: Aminopeptidases and other proteases in the nasal mucosa can partially degrade peptides before absorption

The suitability of nasal delivery depends on the specific peptide, the desired onset of action, the target tissue (peripheral vs central nervous system), and individual patient factors.

Correct administration technique is essential for maximising the effectiveness of intranasal peptides. Poor technique can result in the solution draining into the throat (reducing nasal absorption) or failing to reach the olfactory region (reducing nose-to-brain transport).

Step-by-step technique: 1. Clear your nasal passages — gently blow your nose before administration to remove excess mucus 2. Prime the spray device if it is a new bottle or has not been used recently — pump it several times until a fine mist is produced (direct this away from your face) 3. Tilt your head slightly forward — not backward, as tilting back causes the solution to run down the throat 4. Insert the nozzle into one nostril, angling it slightly toward the outer wall of the nose (away from the septum) 5. Close the opposite nostril with a finger and inhale gently through the nose as you press the pump 6. Avoid sniffing forcefully — a gentle inhalation is sufficient. Forceful sniffing can pull the solution past the nasal cavity and into the throat 7. Hold your breath briefly (3–5 seconds) after spraying to allow the mist to settle on the nasal mucosa 8. Alternate nostrils if multiple sprays are required, allowing 30–60 seconds between sprays

Common mistakes to avoid: - Spraying directly onto the nasal septum, which can cause irritation and nosebleeds - Tilting the head back, which directs the spray away from the absorptive mucosa - Using the spray immediately after blowing your nose vigorously, when the mucosa may be irritated - Failing to prime a new spray device, resulting in an inaccurate initial dose

Peptide nasal sprays require careful attention to storage conditions, as the peptide is already in reconstituted (liquid) form and therefore more susceptible to degradation than lyophilised powder.

Temperature: Most peptide nasal sprays should be stored in the refrigerator at 2–8°C. Some formulations may tolerate brief periods at room temperature (for example, during daily use), but prolonged storage above 8°C will accelerate degradation. Never freeze a nasal spray formulation, as ice crystal formation can damage the peptide structure and the spray mechanism.

Light exposure: Store nasal spray bottles in their original packaging or in a dark location. UV light can cause photodegradation of many peptides. If the spray comes in a clear bottle, consider wrapping it in aluminium foil for additional protection.

Contamination prevention: The nasal spray nozzle is a potential entry point for bacteria. After each use, wipe the nozzle tip with a clean tissue. Avoid touching the nozzle opening with your fingers. Do not share nasal spray devices between individuals, as this creates a cross-contamination risk.

Shelf life: Once opened, most peptide nasal sprays should be used within 4–6 weeks, though this varies by formulation. Check the manufacturer's guidance for the specific product. If the solution becomes cloudy, discoloured, or develops an unusual odour, discard it immediately.

This information is provided for educational purposes only. Peptide nasal sprays discussed here (with the exception of specifically noted approved pharmaceuticals) are research compounds and are not licensed medicines in the UK. Always consult a healthcare professional before using any peptide product.