A peptide supplied as a nasal spray and the same peptide supplied as a lyophilised vial are usually discussed as if the format were packaging. In the published pharmacokinetic literature they are two different experiments. The route changes what fraction of the compound reaches circulation, how fast it is cleared, which tissues see it first, and, for the neuropeptides, whether the brain is reached through the bloodstream at all. Any research protocol that treats the two as interchangeable is making an assumption the literature does not support.
The two routes solve different problems
A subcutaneous or intramuscular injection puts the compound under the skin or into muscle, from which it enters systemic circulation more or less completely. Bioavailability is high and the main variables are absorption rate and clearance. This is why parenteral administration is the default in most animal work: it is the route where dose and exposure have the tightest relationship.
Intranasal administration solves a different problem. Nasal mucosa is thin, densely vascularised, and, critically, carries the olfactory and trigeminal nerve pathways, which run from the nasal cavity directly into the cranial compartment. That anatomy creates a route into the central nervous system that does not require crossing the blood-brain barrier. Agrawal and colleagues, reviewing nose-to-brain delivery in 2018, describe this as the principal reason the route attracted attention for centrally acting compounds: material deposited on the olfactory epithelium can reach the brain while bypassing both first-pass metabolism and the barrier that excludes most peptides from the CNS.
What the route costs
The trade is not free. The same review, and Md and colleagues before it, identify the constraints plainly: nasal mucosal permeability is limited, the volume that can be deposited is small, and mucociliary clearance sweeps material toward the pharynx within minutes. Peptidases in the nasal mucosa degrade many peptides on contact. The practical consequence is that intranasal bioavailability, measured as a percentage of the administered dose reaching systemic circulation, is generally low, and far more variable between studies than injection.
So the honest summary of the two routes is not "one is better". It is that injection buys reliable systemic exposure, and intranasal buys a possible direct CNS pathway at the cost of much lower and less predictable total delivery.
The numbers are compound-specific, and mostly absent
This is where the general argument has to stop. Route behaviour depends on molecular weight, charge, lipophilicity and susceptibility to local peptidases, and those differ per compound. A published intranasal figure for one peptide says nothing quantitative about another.
For a few compounds the work exists. Tritium-labelled Semax was tracked into rat brain within two minutes of intranasal dosing. Intranasal NAD+ has been shown to raise brain NAD+ content in mice. Both are real measurements in animals.
For most of the catalogue it does not exist. There is no published intranasal pharmacokinetic study for the majority of research peptides sold in spray format, including several where the spray is the more popular presentation. That absence is a fact about the literature, not a defect in the compound, but it does mean a protocol cannot cite a bioavailability figure it does not have.
What a comparison can and cannot establish
Three limits are worth stating directly.
First, delivery is not effect. Tsuchiyama and colleagues showed intranasal NAD+ raising brain NAD+ content in mice and, in the same experiment, failing to improve outcome after intracerebral haemorrhage. Getting a molecule to the tissue and changing the biology are separate claims requiring separate evidence.
Second, animal nasal anatomy is not human nasal anatomy. Rodents have proportionally far more olfactory epithelium than humans do, which is precisely the surface the nose-to-brain route depends on. Rodent intranasal results are a weak basis for quantitative human extrapolation.
Third, almost none of this work is dose-equivalence work. Studies that administer a compound intranasally and studies that inject it were generally designed to answer different questions, in different models, at different doses. They do not license converting one into the other.
The takeaway
Route of administration is a variable in the experiment, not a packaging choice. Injection is the better-characterised route with higher and more reproducible systemic exposure. Intranasal delivery offers a documented anatomical path to the CNS with lower and more variable total delivery, and with published pharmacokinetics for only a handful of compounds. We stock both formats across the catalogue, the nasal spray line and the vial line, because the published research treats them as distinct, and a protocol should record which one it used rather than assume the two are equivalent.
All products are intended for research use only. Not for human consumption. Must be 21 years of age or older to purchase.
References
1. Agrawal, M., Saraf, S., Saraf, S., et al. (2018). Nose-to-brain drug delivery: An update on clinical challenges and progress towards approval of anti-Alzheimer drugs. Journal of Controlled Release, 281, 139-177. https://doi.org/10.1016/j.jconrel.2018.05.011
2. Md, S., Mustafa, G., Baboota, S., & Ali, J. (2015). Nanoneurotherapeutics approach intended for direct nose to brain delivery. Drug Development and Industrial Pharmacy, 41(12), 1922-1934. https://doi.org/10.3109/03639045.2015.1052081
3. Agrawal, M., Saraf, S., Saraf, S., et al. (2020). Stimuli-responsive In situ gelling system for nose-to-brain drug delivery. Journal of Controlled Release, 327, 235-265. https://doi.org/10.1016/j.jconrel.2020.07.044
4. Shevchenko, K. V., Nagaev, I. Yu., Alfeeva, L. Yu., et al. (2006). Kinetics of Semax penetration into the brain and blood of rats after its intranasal administration. Bioorganicheskaia Khimiia, 32(1), 64-70. https://doi.org/10.1134/s1068162006010055
5. Tsuchiyama, R., Sozen, T., Manaenko, A., Zhang, J. H., & Tang, J. (2009). The effects of nicotinamide adenine dinucleotide on intracerebral hemorrhage-induced brain injury in mice. Neurological Research, 31(2), 179-182. https://doi.org/10.1179/174313209X393609
