Peptide Nasal Sprays vs. Injections: Delivery Methods

Selank, a small anxiolytic peptide weighing just 751 daltons, achieves 92.8% bioavailability through nasal spray — nearly matching what an injection delivers. Most peptides are not this fortunate. The typical nasal spray gets less than 5% of the peptide into your bloodstream. Injections routinely deliver close to 100%.

That gap defines the central tension between these two delivery methods. Nasal sprays are painless, convenient, and needle-free. Injections are reliable, well-characterized, and dramatically more effective at getting peptides where they need to go. For peptides like BPC-157, semaglutide, and CJC-1295, understanding this trade-off matters.

But the story is more nuanced than "injections always win." Nasal delivery offers one advantage that needles cannot match: a direct route to the brain. For peptides targeting neurological conditions — oxytocin for social behavior, insulin for Alzheimer's research, Selank for anxiety — the nose-to-brain pathway bypasses the blood-brain barrier entirely. That is something no injection can do.

This guide breaks down the science of both delivery routes, compares bioavailability data, and helps you understand when each method makes sense.

Table of Contents

• How Nasal Spray Delivery Works
• How Injectable Delivery Works
• Bioavailability: The Numbers That Matter
• The Nose-to-Brain Pathway
• Molecular Weight and Nasal Success
• Peptide-Specific Comparisons
• Absorption Enhancers and Emerging Technology
• Practical Considerations
• Cost Comparison
• Head-to-Head Comparison Table
• The Bottom Line
• References

How Nasal Spray Delivery Works

The nasal cavity is more than a passageway for air. Its interior is lined with highly vascularized tissue — a dense network of blood vessels just beneath a thin mucosal membrane. This creates a large surface area (approximately 150-180 cm^2) where molecules can cross directly into the bloodstream.

When a peptide nasal spray enters the nose, it encounters three distinct regions:

The vestibule — The outermost area, lined with skin-like tissue. Poor absorption site. Most spray that lands here is wasted.

The respiratory region — The largest area, covering roughly 90% of the nasal cavity. Rich in blood vessels. This is where most systemic absorption occurs. Peptides cross the mucosal membrane and enter the bloodstream, bypassing the liver's first-pass metabolism.

The olfactory region — A small area (just 3-5% of the nasal cavity surface) in the upper nasal passages. This region connects directly to the brain via olfactory nerve fibers, creating the nose-to-brain pathway. Peptides that reach this region can potentially access the central nervous system without crossing the blood-brain barrier.

Why Nasal Delivery Is Difficult for Peptides

Despite the nasal cavity's absorptive potential, several barriers limit peptide bioavailability:

Mucociliary clearance. The nasal mucosa constantly produces mucus that moves toward the throat at a rate that clears most deposited material within 15-20 minutes. This gives the peptide a narrow window for absorption.

Enzymatic degradation. The nasal mucosa contains proteolytic enzymes that break down peptides before they can cross the membrane. This is less aggressive than the GI tract's enzymatic environment but still significant.

Membrane permeability. Peptides are generally hydrophilic (water-loving) molecules with limited ability to cross lipid cell membranes. Larger peptides face greater difficulty crossing the mucosal barrier.

Limited volume. The nasal cavity can hold only about 150-200 microliters per nostril before runoff occurs. This limits the dose that can be effectively delivered.

pH sensitivity. The nasal cavity maintains a pH of 5.5-6.5. Formulations outside this range can cause irritation and further reduce absorption. Peptides may also degrade at suboptimal pH.

How Injectable Delivery Works

Injections deliver peptides directly into the body, bypassing every absorption barrier. The two most common routes for peptide injections are subcutaneous (SC) and intramuscular (IM).

Subcutaneous injection places the peptide into the fatty tissue beneath the skin. Absorption is gradual, producing sustained blood levels over hours. This is the standard delivery method for most therapeutic peptides including GLP-1 agonists, growth hormone–releasing peptides, and healing peptides like BPC-157.

Intramuscular injection delivers the peptide into muscle tissue, where higher blood flow produces faster absorption and a quicker peak.

Both routes provide near-complete bioavailability for most peptides. There is no enzymatic barrier, no mucociliary clearance, and no absorption window. What you inject reaches the bloodstream.

The trade-off is obvious: injections require needles, sterile technique, reconstitution of lyophilized peptides, proper storage, and some degree of training. Many people are uncomfortable with self-injection. Some cannot do it at all.

Bioavailability: The Numbers That Matter

This is where the two methods diverge most dramatically. Bioavailability measures the percentage of the administered dose that reaches systemic circulation in an active form.

Peptide Bioavailability by Route

Peptide	Molecular Weight	Nasal Bioavailability	Injectable Bioavailability
Selank	751 Da	92.8%	~100%
GHRP-2	817 Da	~50%	~100%
Ipamorelin	711 Da	~20%	~100%
Desmopressin (DDAVP)	1,069 Da	3-5%	~100%
Oxytocin	1,007 Da	Varies (debated)	~100%
Calcitonin	3,432 Da	~3%	~100%
Insulin	5,808 Da	<1-3% (without enhancers)	~100%
Most peptides >6 kDa	>6,000 Da	<1-5%	~100%

Several patterns emerge from this data:

1. Small peptides (under ~1 kDa) can achieve good nasal bioavailability. Selank at 92.8% and GHRP-2 at 50% show that the nasal route works well for certain small peptides.

2. Bioavailability drops sharply as molecular weight increases. Calcitonin at 3.4 kDa achieves only ~3%. Insulin at 5.8 kDa struggles below 3% without enhancement technology.

3. The general threshold is about 6,000 daltons. Above this molecular weight, nasal delivery rarely achieves clinically useful bioavailability without specialized formulation technology.

4. Injectables maintain near-100% bioavailability regardless of peptide size. This consistency is their fundamental advantage.

The Nose-to-Brain Pathway

Nasal delivery's most unique advantage has nothing to do with systemic bioavailability. It is the ability to deliver peptides directly to the brain through the olfactory and trigeminal nerve pathways.

The olfactory region sits at the top of the nasal cavity, separated from the brain by only a thin layer of tissue called the cribriform plate. Peptides deposited in this region can travel along olfactory nerve fibers directly into the brain, bypassing the blood-brain barrier (BBB) entirely.

This matters because the BBB blocks most peptides from entering the brain after systemic administration. A peptide injected subcutaneously must circulate through the entire body, and the BBB will prevent most of it from reaching brain tissue.

Oxytocin: A Case Study

Oxytocin is the most studied peptide for intranasal brain delivery. Used in research on social behavior, autism, anxiety, and bonding, intranasal oxytocin has been the preferred delivery route in hundreds of clinical studies.

However, the evidence is more complex than the hype suggests. A study in rhesus macaques published in Molecular Psychiatry found that both intranasal and intravenous oxytocin reached the cerebrospinal fluid (CSF) within one hour of administration — and there was no increased bioavailability of oxytocin in the CSF after intranasal delivery compared to intravenous delivery.

This raises questions about whether intranasal oxytocin actually reaches the brain through a special nose-to-brain pathway or simply through systemic circulation, like an injection would. The debate continues in the scientific community.

Where Nose-to-Brain Shows Promise

Despite the oxytocin controversy, intranasal delivery has shown genuine promise for certain CNS-targeted applications:

• Insulin for Alzheimer's research — Intranasal insulin has been studied for cognitive enhancement and neuroprotection. Cell-penetrating peptides (CPPs) have improved intranasal insulin delivery in animal models.
• Selank and Semax — These Russian-developed nootropic peptides were specifically designed for intranasal delivery and achieve clinically meaningful brain concentrations via this route.
• Erythropoietin — A much larger molecule (30,000 Da), intranasal EPO achieved 14-28% bioavailability in rat studies using specialized delivery technology.

Molecular Weight and Nasal Success

The 6,000-dalton cutoff is a guideline, not a hard rule. Several factors beyond molecular weight determine whether a peptide works nasally:

Lipophilicity. Peptides with some hydrophobic character cross mucosal membranes more easily than purely hydrophilic ones.

Charge. Charged peptides interact differently with the nasal mucosa. Some charges improve mucoadhesion (sticking to the nasal lining), extending the absorption window.

Structural stability. Peptides resistant to enzymatic degradation in the nasal cavity achieve higher bioavailability because more of the dose survives long enough to be absorbed.

Formulation. The vehicle matters enormously. A peptide that achieves 1% bioavailability in a simple saline spray might achieve 10-20% with the right absorption enhancers, mucoadhesive agents, or nanoparticle carriers.

Peptide-Specific Comparisons

BPC-157

Injectable bioavailability: High (standard SC/IM delivery) Nasal bioavailability: Unknown — no published pharmacokinetic studies

BPC-157 is a 15-amino acid peptide with a molecular weight of approximately 1,419 daltons. Based on its size alone, it falls within the range where nasal absorption is theoretically possible but likely limited.

No peer-reviewed study has examined BPC-157 administered intranasally. The more than 30 preclinical studies examining BPC-157 used injection-based routes (IM, IV, IP) or oral administration. No dose-ranging studies have examined what plasma concentrations can be achieved with nasal BPC-157.

One study found that topical BPC-157 reduced brain swelling in rats with sagittal sinus thrombosis. Another found anti-inflammatory effects from intranasal BPC-157 in rats with rhinitis. But these are preliminary animal findings, not pharmacokinetic data.

For systemic tissue repair — the most common use case for BPC-157 — subcutaneous injection near the injury site remains the better-supported approach. Nasal BPC-157 may have a role in CNS-related applications, but the evidence base is currently too thin to draw strong conclusions.

Semaglutide

Injectable bioavailability: ~89% (SC) Oral bioavailability: ~1% (with SNAC absorption enhancer) Nasal bioavailability: Not commercially developed

Semaglutide at approximately 4,114 daltons is too large for efficient nasal absorption without significant formulation technology. Even oral semaglutide (Rybelsus) requires a specialized absorption enhancer (SNAC — sodium N-[8-(2-hydroxybenzoyl)amino] caprylate) and still achieves only about 1% bioavailability.

The injectable route remains the gold standard for semaglutide. The new oral formulation (Wegovy pill, approved December 2025) offers a needle-free alternative, though at much higher doses (50 mg oral vs. 2.4 mg injectable) to compensate for low oral bioavailability.

CJC-1295

Injectable bioavailability: High (standard SC delivery) Nasal bioavailability: No published data

CJC-1295 is a 30-amino acid modified GHRH analog with a molecular weight of approximately 3,368 daltons. Its size puts it in a challenging range for nasal delivery. The Drug Affinity Complex (DAC) modification that extends its half-life through albumin binding would likely be even less amenable to nasal absorption due to increased molecular complexity.

SC injection remains the standard and best-supported route for CJC-1295.

Growth Hormone–Releasing Peptides

GHRP-2 nasal bioavailability: ~50% Ipamorelin nasal bioavailability: ~20%

These are among the best-performing peptides for nasal delivery. Their small molecular weights (GHRP-2: 817 Da; Ipamorelin: 711 Da) allow them to cross the nasal mucosa relatively efficiently.

For GHRP-2, the 50% nasal bioavailability means you would need roughly double the nasal dose compared to injection to achieve equivalent systemic exposure. That is a workable ratio. For ipamorelin at 20%, you would need approximately five times the nasal dose — still feasible but less efficient.

Oxytocin

Injectable bioavailability: ~100% (IV/IM) Nasal bioavailability: Debated (2-5% systemically; CNS access via nose-to-brain unclear)

Intranasal oxytocin (Syntocinon) is one of the few FDA-approved nasal peptide products. It is used clinically to promote milk letdown during breastfeeding and has been studied extensively for behavioral and psychiatric applications.

The systemic bioavailability of nasal oxytocin is low. But the clinical interest is not in systemic levels — it is in brain delivery via the nose-to-brain pathway. As discussed above, the evidence for this pathway remains controversial.

Absorption Enhancers and Emerging Technology

The nasal delivery field is actively working to close the bioavailability gap. Several technologies show promise:

Absorption Enhancers

Certain molecules can temporarily increase the permeability of the nasal mucosa, allowing larger peptides to cross more effectively:

• Alkyl saccharides (e.g., Intravail) — A class of non-irritating absorption enhancers that have shown the ability to dramatically improve nasal peptide bioavailability. Molecules as large as erythropoietin (30,000 Da) achieved 14-28% nasal bioavailability in rat studies using these enhancers.
• Chitosan — A natural polymer derived from crustacean shells that acts as both a mucoadhesive (extending contact time) and a permeation enhancer (opening tight junctions between cells).
• Cell-penetrating peptides (CPPs) — Short peptide sequences that facilitate transport across cell membranes. They have been applied to nasal delivery of insulin and exendin-4 for both diabetes and Alzheimer's research.

Nanoparticle Carriers

Nanoparticles — made from lipids, polymers, or proteins — can encapsulate peptides and protect them from enzymatic degradation while improving membrane permeation:

• Lipid nanoparticles — Mimic cell membrane composition, facilitating mucosal uptake
• Polymeric nanoparticles — Provide sustained release and protection from degradation
• Liposomes — Vesicular carriers that improve peptide stability and absorption

These carriers can extend the contact time of the peptide with the nasal mucosa (combating mucociliary clearance) and protect the peptide from enzymatic breakdown.

Mucoadhesive Systems

Formulations that stick to the nasal mucosa extend the absorption window beyond the typical 15-20 minute mucociliary clearance cycle. Mucoadhesive polymers like carbopol, hyaluronic acid, and cellulose derivatives can keep the peptide in contact with absorptive tissue for hours instead of minutes.

Specialized Delivery Devices

Standard nasal spray bottles deposit most of their payload in the lower nasal cavity (respiratory region). Advanced devices aim to target the olfactory region specifically:

• Precision olfactory delivery (POD) devices — Designed to deposit spray in the upper nasal cavity near the olfactory region
• Bi-directional delivery devices — Use one nostril for air input and the other for spray delivery, targeting deeper nasal regions
• Nebulizers — Produce finer particles that can reach the olfactory region more effectively

These technologies are still largely in research and early clinical stages, but they represent the direction of the field.

Practical Considerations

Patient Experience

Factor	Nasal Spray	Injection
Pain	None	Minimal (SC) to moderate (IM)
Needle anxiety	Not applicable	Common barrier for many patients
Preparation time	Seconds	5-10 minutes (including reconstitution)
Sterile technique	Minimal	Required
Training needed	Minimal	Moderate
Self-administration	Very easy	Easy (SC) to moderate (IM)
Travel convenience	High (no sharps)	Lower (needles, vials, cold storage)
Frequency	Often 2-3x daily	Often 1x daily or 1x weekly

Research on patient preferences consistently shows a strong preference for nasal formulations. The elimination of needle-related anxiety, pain, and the need for sterile technique reduces barriers to consistent adherence.

Storage and Stability

Nasal peptide sprays are generally more stable than reconstituted injectable peptides because many come in preserved, ready-to-use formulations. However, some nasal peptide products require refrigeration and have limited shelf lives once opened.

Injectable peptides — particularly lyophilized formulations — can be stored for months to years before reconstitution. Once reconstituted, they typically last 2-4 weeks refrigerated.

Dosing Precision

Injectable delivery offers superior dosing precision. A calibrated syringe delivers an exact volume, and the near-100% bioavailability means the dose you measure is essentially the dose that reaches your blood.

Nasal sprays introduce variability at multiple points: spray volume per actuation, deposition pattern in the nasal cavity, mucociliary clearance rate, and individual differences in nasal anatomy and congestion. Two people using the same nasal spray may absorb significantly different amounts.

Nasal Congestion

This is a practical limitation often overlooked. If you have a cold, allergies, or chronic sinusitis, nasal congestion can dramatically reduce absorption. Swollen mucosa, excess mucus, and altered blood flow all impair nasal peptide delivery. Injections are unaffected by nasal congestion.

Cost Comparison

Factor	Nasal Spray	Injection
Per-dose cost	Often higher (more peptide needed)	Often lower (higher bioavailability)
Ancillary costs	Minimal (spray device)	Syringes, needles, alcohol swabs, bacteriostatic water
Example: NAD+ monthly	$144-199	$155-235
Hidden cost	More peptide per dose to compensate for low bioavailability	Reconstitution supplies

The price differential between nasal and injectable formulations often reflects the bioavailability gap. A nasal spray may contain two to five times more peptide per dose than an injection to achieve a comparable effect. When the nasal bioavailability is very low (under 5%), the amount of peptide needed to compensate can make nasal delivery the more expensive option per effective dose — even if the sticker price per unit looks similar.

Head-to-Head Comparison Table

Feature	Nasal Spray	Injection (SC/IM)
Systemic bioavailability	<5% (most peptides); up to 92.8% (small peptides)	65-100%
Brain access	Direct nose-to-brain pathway possible	Blocked by blood-brain barrier
Best molecular weight range	Under 6,000 Da	Any size
Onset of action	Fast (minutes)	Fast (SC: 30-90 min; IM: 15-60 min)
Patient convenience	Very high	Moderate
Dosing precision	Variable	High
Needle required	No	Yes
Affected by congestion	Yes	No
Sterile technique	Minimal	Required
FDA-approved peptide products	Few (oxytocin, desmopressin, calcitonin)	Many
Research maturity	Growing	Well-established

The Bottom Line

For most therapeutic peptides, injections remain the gold standard. The near-100% bioavailability, precise dosing, and extensive clinical evidence supporting injectable delivery make it the reliable choice for systemic peptide therapy. If you need a peptide to reach tissues throughout your body — whether for metabolic, healing, hormonal, or anti-aging purposes — subcutaneous injection is the better-supported route.

Nasal sprays have their place, but it is more specific than many marketing claims suggest. They work best for:

1. Small peptides under 1,000 Da that achieve reasonable nasal bioavailability (Selank, GHRP-2, Ipamorelin)
2. CNS-targeted peptides where the nose-to-brain pathway offers a genuine advantage over systemic delivery (though evidence is still developing for most)
3. Patients who truly cannot tolerate injections and need an alternative, even at reduced efficacy

The technology gap is narrowing. Absorption enhancers, nanoparticle carriers, and specialized delivery devices are improving nasal bioavailability for larger peptides. Within the next decade, the nasal route may become viable for a much broader range of peptide therapeutics. But today, for most peptides most people use, the needle still delivers more medicine more reliably.

Talk to your healthcare provider about which delivery route makes sense for your specific peptide, therapeutic goals, and personal preferences. The best delivery method is the one that balances efficacy, convenience, and adherence for your individual situation.

References

1. Alabsi W, et al. "Nose-to-Brain Delivery of Therapeutic Peptides as Nasal Aerosols." Pharmaceutics. 2022;14(9):1870. https://pmc.ncbi.nlm.nih.gov/articles/PMC9502087/

2. Shingaki T, et al. "A comprehensive review of advanced nasal delivery: Specially insulin and calcitonin." Journal of Drug Delivery Science and Technology. 2023. https://www.sciencedirect.com/science/article/pii/S0928098723002609

3. Modi S, et al. "Overview of intranasally delivered peptides: key considerations for pharmaceutical development." Expert Opinion on Drug Delivery. 2018;15(10):977-989. https://pubmed.ncbi.nlm.nih.gov/30173579/

4. Lee MR, et al. "Oxytocin by intranasal and intravenous routes reaches the cerebrospinal fluid in rhesus macaques: determination using a novel oxytocin assay." Molecular Psychiatry. 2018;23:115-122. https://pmc.ncbi.nlm.nih.gov/articles/PMC5862033/

5. Wang M, et al. "Systemic and brain delivery of antidiabetic peptides through nasal administration using cell-penetrating peptides." Frontiers in Pharmacology. 2022;13:1068495. https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.1068495/full

6. Bachem. "Bioavailability of peptides." https://www.bachem.com/articles/peptides/bioavailability-of-peptides/

7. Maggio ET. "Intravail: Highly effective intranasal delivery of peptide and protein drugs." Expert Opinion on Drug Delivery. 2006. https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=650bd67274bf0a89172c295fa49cd4f978cd4c89

8. Jay Campbell. "Peptide Nasal Spray vs Injection: Delivery Methods Compared." https://jaycampbell.com/peptides/peptide-nasal-spray-vs-injection/

9. Peptides.org. "BPC-157 Nasal Spray vs. Injections: Comprehensive Comparison." https://www.peptides.org/bpc-157-nasal-spray-vs-injections/

10. Swolverine. "Peptide Delivery Methods: Injections vs Oral vs Nanoparticles Explained." https://swolverine.com/blogs/blog/peptide-delivery-methods-injections-vs-oral-vs-nanoparticles-explained