Why do some peptides have to be injected while others can be oral or intranasal?

Many peptides are broken down by digestive enzymes and cross the gut lining poorly. An injection bypasses the digestive tract, making meaningful exposure easier to achieve for some molecules. Bioavailability is the fraction of an administered dose that reaches the circulation intact; it can differ dramatically between routes. This is why swallowing a peptide does not automatically reproduce the effect of injecting it.[1]

Oral delivery can work when the molecule and formulation solve enough of those barriers. Oral semaglutide uses the absorption enhancer SNAC to support uptake through the stomach lining. Clinical pharmacology studies show that food, water, and timing can affect exposure, and only a small fraction of the swallowed dose is absorbed. Its success does not validate arbitrary oral versions of other peptides, or prove that the same milligram amount is equivalent across routes.[1][2]

Intranasal delivery uses the nasal lining instead of the gut, but absorption remains molecule- and formulation-dependent. Desmopressin is an established example with oral and nasal products that differ markedly in bioavailability; nasal abnormalities can also affect absorption. A nasal spray is therefore not automatically more effective or a proven shortcut into the brain. Each route needs its own evidence for exposure, benefit, and safety.[3]