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.
Intranasal (i.n.) administration of IFN beta-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 (i.v.) administration of IFN beta-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 IFN beta-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.
Ross
T M
TM
Alzheimer's Research Center, Regions Hospital, 640 Jackson St., St. Paul, MN 55101, USA.
Martinez
P M
PM
Renner
J C
JC
Thorne
R G
RG
Hanson
L R
LR
Frey
W H
WH
D000281:Administration, Intranasal; D000818:Animals; D001345:Autoradiography; D001812:Blood-Brain Barrier / Q000502:physiology*; D015153:Blotting, Western; D001923:Brain Chemistry; D002490:Central Nervous System / Q000737:chemistry* / Q000378:metabolism; D002574:Cervical Vertebrae; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000378:metabolism; D007275:Injections, Intravenous; D016899:Interferon-beta / Q000008:administration & dosage* / Q000378:metabolism; D008198:Lymph Nodes; D008297:Male; D009103:Multiple Sclerosis / Q000188:drug therapy*; D051381:Rats; D014018:Tissue Distribution
D007166:Immunosuppressive Agents; D016899:Interferon-beta