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Direct contact between the peptide and esophageal tissue during swallowing provides local exposure in addition to systemic effects achieved after absorption

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Furthermore, indirect data suggest that barrier defect might precede the onset of disease (316) and up to 40% of first-degree relatives of patients with Crohn's disease demonstrate an altered small intestinal permeability (317)

doi: 10.1093/intimm/13.4.397 5 MalavasiFDeaglioSFunaroAFerreroEHorensteinALOrtolanEet al

Intranasal delivery extends the effective CNS half life because the peptide is transported directly along olfactory and trigeminal nerve pathways into cerebrospinal fluid and hippocampal interstitial space, bypassing systemic circulation and hepatic metabolism

Huang, Y., Cohen, J