Intranasal Delivery
Intranasal delivery uses the nasal mucosa as an absorption surface, offering needle-free administration and rapid onset but low and variable bioavailability for peptides.
The nasal cavity offers a richly vascularised mucosa draining directly into the systemic circulation, bypassing hepatic first-pass metabolism. Against that it is defended: a mucus layer, cilia that clear deposited material toward the throat within minutes, and mucosal peptidases that degrade peptides in place. The result is that small lipophilic molecules can be absorbed nasally with high efficiency, while peptides of even modest size are absorbed at a small percentage of what is administered unless a permeation enhancer is included.
Several approved products nonetheless use the route. Desmopressin, calcitonin, nafarelin and buserelin have all been marketed as nasal sprays, and naloxone nasal spray became the standard lay-administered opioid reversal product. Oxytocin nasal preparations are used clinically and extensively in behavioural research. The common thread is potency: low fractional absorption is still sufficient, and the route was chosen for speed or convenience rather than efficiency.
The tradeoff is speed against reliability. Nasal absorption can be fast, but deposition depends on device geometry, spray plume, head position and the state of the mucosa, so a cold, allergic rhinitis or recent nasal surgery changes exposure in ways hard to quantify. Variability of that size is tolerable for a drug with a wide therapeutic window and poorly tolerable for one needing consistent exposure.
The claim needing most scrutiny is nose-to-brain transport. There is a genuine anatomical basis, since olfactory and trigeminal pathways can carry a small fraction of material toward the central nervous system without crossing the blood-brain barrier, but the fraction demonstrated in humans is very small and much supporting work is rodent, where olfactory epithelium occupies a far greater share of the nasal cavity.