Intranasal administration of interferon beta bypasses the blood–brain barrier to target the central nervous system and cervical lymph nodes: a non-invasive treatment strategy for multiple sclerosis

• Published in: Journal of neuroimmunology Vol. 151; no. 1; pp. 66 - 77
• Main Authors: Ross, T.M, Martinez, P.M, Renner, J.C, Thorne, R.G, Hanson, L.R, Frey, W.H
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2004
• Subjects: Administration, Intranasal; Animals; Autoradiography; Blood-Brain Barrier - physiology; Blood–brain barrier; Blotting, Western; Brain Chemistry; Central Nervous System - chemistry; Central Nervous System - metabolism; Cervical Vertebrae; Cytokines; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - metabolism; Injections, Intravenous; Interferon-beta - administration & dosage; Interferon-beta - metabolism; Interferon-β; Intranasal; Lymph Nodes; Male; Multiple sclerosis; Multiple Sclerosis - drug therapy; Rats; Tissue Distribution; Interferon-β; Multiple sclerosis; Intranasal; Cytokines; Blood–brain barrier
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/j.jneuroim.2004.02.011

Intranasal (IN) administration of IFNβ-1b was examined as a route for targeted delivery to the rat central nervous system (CNS). Intranasal administration resulted in significant delivery throughout the CNS and cervical lymph nodes with low delivery to peripheral organs. At similar blood levels, intravenous (IV) administration of IFNβ-1b yielded 88–98% lower CNS levels and 100–1650% greater peripheral organ levels compared to intranasal. Autoradiography confirmed much greater delivery to the CNS with intranasal administration. Intranasally administered IFNβ-1b reached the brain intact and produced tyrosine phosphorylation of IFN receptor in the CNS. Intranasal administration offers a non-invasive method of drug delivery for multiple sclerosis (MS) that bypasses the blood–brain barrier (BBB) and directly targets the CNS and lymph nodes.