Intranasal delivery of insulin via the olfactory nerve pathway
Abstract
Objectives: 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. Key findings: 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.
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The limited number of routes to reach the brain, such as blood-brain barrier and extraneuronal/perineuronal routes along the trigeminal or olfactory nerves, likely explains why only a small amount of intranasal oxytocin reaches the brain.
“This is likely because of the limited number of routes to reach the brain, such as blood-brain barrier and extraneuronal/perineuronal routes along the trigeminal or olfactory nerves.10, 49, 50, 51, 52, 53”
From Oxytocin efficacy is modulated by dosage and oxytocin receptor genotype in young adults with high-functioning autism: a 24-week randomized clinical trial (2016) · cites this paper as [53]
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- Authors
- Renner, D. B., Svitak, A. L., Gallus, N. J., Ericson, M. E., Frey, W. H., & Hanson, L. R.
- Affiliations
- Regions Hospital (US)
- Corresponding author
- Renner, Dan B
- Venue
- Journal of Pharmacy and Pharmacology
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-12-01
- Volume
- 64
- Issue
- 12
- Pages
- 1709-1714
- ISSN
- 0022-3573 (ISSN-L)
- 2042-7158
- OpenAlex
- W1612293997
- Cited by
- 116
- References
- 24
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 11 · 2023: 14 · 2022: 7 · 2021: 13 · 2020: 9 · 2019: 7 · 2018: 7 · 2017: 10 · 2016: 4 · 2015: 7 · 2014: 9 · 2013: 6 · 2012: 1
- FWCI
- 4.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Journal of Pharmacy and Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Life Sciences › Neuroscience › Sensory Systems › Olfactory and Sensory Function Studies
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
- Keywords
- olfactory bulb, olfactory epithelium, central nervous system targeting, peptide therapeutics, cribriform plate, glomerular layer, intranasal drug delivery
- MeSH terms
- Administration, Intranasal, Animals, Central Nervous System, Ethmoid Bone, Insulin, Male, Mice, Inbred C57BL, Microscopy, Nasal Mucosa, Olfactory Bulb, Olfactory Nerve, Olfactory Pathways, Mice
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