title: Intranasal delivery of insulin via the olfactory nerve pathway.
abstract: OBJECTIVE
  Intranasal delivery has been shown to target peptide therapeutics to the central nervous system (CNS) of animal models and induce specific neurological responses. In an investigation into the pathways by which intranasal administration delivers insulin to the CNS, this study has focused on the direct delivery of insulin from the olfactory mucosa to the olfactory bulbs via the olfactory nerve pathway.
  
  
  METHODS
  Nasal and olfactory tissues of mice were imaged with fluorescent and electron microscopy 30 min following intranasal administration.
  
  
  RESULTS
  Macroscopic analysis confirmed delivery to the anterior regions of the olfactory bulbs. Confocal microscopy captured delivery along the olfactory nerve bundles exiting the nasal mucosa, traversing the cribriform plate and entering the bulbs. With electron microscopy, insulin was found within cells of the olfactory nerve layer and glomerular layer of the olfactory bulbs.
  
  
  CONCLUSIONS
  These results demonstrated that intranasal administration of labelled insulin targeted the CNS through the olfactory nerve pathway in mice.
authors.affiliation: Alzheimer's Research Center at Regions Hospital, HealthPartners Research Foundation, St Paul, MN 55101, USA. dan.b.renner@healthpartners.com
authors.forename: Dan B
authors.initials: DB
authors.lastname: Renner
authors.forename: Aleta L
authors.initials: AL
authors.lastname: Svitak
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Gallus
authors.forename: Marna E
authors.initials: ME
authors.lastname: Ericson
authors.forename: William H
authors.initials: WH
authors.lastname: Frey
authors.forename: Leah R
authors.initials: LR
authors.lastname: Hanson
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D002490:Central Nervous System / Q000378:metabolism; D005004:Ethmoid Bone / Q000378:metabolism; D007328:Insulin / Q000008:administration & dosage* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008853:Microscopy / Q000379:methods; D009297:Nasal Mucosa / Q000378:metabolism*; D009830:Olfactory Bulb / Q000378:metabolism; D009832:Olfactory Nerve / Q000378:metabolism*; D009833:Olfactory Pathways / Q000378:metabolism*
chemical_list: D007328:Insulin