Intranasal route
also: intranasal delivery, nasal spray peptides, nose-to-brain delivery, IN route
Administration of a peptide solution via nasal spray to achieve direct transport along olfactory and trigeminal nerve pathways into the CNS, bypassing the blood-brain barrier.
Intranasal (IN) administration involves applying a liquid or powder formulation directly to the nasal mucosa, typically using a nasal spray atomiser. While some of the absorbed dose enters systemic circulation via nasal mucosal vasculature, the primary interest of intranasal delivery for CNS-active peptides is the nose-to-brain pathway: drug molecules deposited on the olfactory and trigeminal nerve endings in the upper nasal cavity can be transported into the central nervous system along perineural and perivascular channels, partially circumventing the blood-brain barrier (BBB).
Why it matters in peptide research
Most peptides are too hydrophilic, too large, or too susceptible to enzymatic degradation to achieve meaningful CNS concentrations after peripheral (SC or IV) injection because the BBB restricts passive diffusion of large polar molecules. Intranasal delivery offers an alternative anatomical access route for peptides that have CNS targets but limited BBB permeability. Olfactory ensheathing cells and olfactory nerve fascicles that terminate in the olfactory bulb create a semi-open channel between the nasal cavity and the subarachnoid space, allowing small volumes of peptide solution to reach the CNS without first entering systemic circulation.
Semax and Selank are the canonical examples of intranasal peptide administration in the research community. Both are Russian-developed neuropeptides designed and clinically validated as nasal sprays; their CNS bioavailability via the intranasal route substantially exceeds what would be expected from systemic absorption alone. Semax (an ACTH 4-10 analogue with Pro-Gly-Pro extension) and Selank (a tuftsin analogue with Gly-Pro extension) have both been studied in Russian clinical trials primarily as intranasal formulations, making IN the evidence-matched route for these compounds.
Practical intranasal technique for research peptides involves using a mucosal atomisation device (MAD) or a purpose-built nasal spray vial, tilting the head slightly forward, spraying while inhaling gently, and alternating nostrils to maximise mucosal contact area. The typical delivered volume per actuation is 100 mcL — a meaningful constraint for calculating concentration and per-dose quantity.
Peptides / stacks that act on this
- Semax — ACTH-analogue neuropeptide developed and clinically validated as an intranasal formulation; standard route for all published Russian clinical data
- Selank — tuftsin-analogue anxiolytic neuropeptide; intranasal administration is the primary delivery route in published research
Common misconceptions
Intranasal delivery does not guarantee CNS penetration — it provides access to the nose-to-brain pathway, but the fraction of dose that actually reaches CNS targets via this route is variable and depends on molecular weight, formulation, nasal deposition pattern, and nasal mucosa condition. Nasal congestion, rhinitis, or mucosal atrophy can substantially reduce effective delivery, making IN an inherently more variable route than SC injection.