Intranasal administration delivers peptoids to the rat central nervous system

Intranasal administration of therapeutic agents offers a noninvasive method of drug delivery that bypasses the blood–brain barrier and directly targets the central nervous system (CNS) and lymph nodes. We examined whether intranasal peptoid CHIR5585, an antagonist of the urokinase plasminogen activator receptor (uPAR), is delivered to the CNS. Peptoids are a novel class of peptide isomers that are oligomeric N-substituted glycine peptides. Anesthetized male rats were administered peptoid CHIR5585 intranasally, and tissue distribution was evaluated quantitatively by gamma counting and qualitatively by autoradiography. Intranasal administration resulted in significant delivery throughout the CNS (olfactory bulbs, 3.9 μM; cortex, 0.3 μM; trigeminal nerve, 1.7 μM) and deep cervical lymph nodes (4.5 μM). Autoradiography demonstrated a similar delivery pattern to the CNS.