The DOI matches its Crossref record; 22 of the 24 references it cites were found in a registry or an index.
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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“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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1 retracted
Francis, G. J., Martinez, J. A., Liu, W. Q., Xu, K., Ayer, A. B., Fine, J. M., Tuor, U. I., Glazner, G. W., Hanson, L. R., Frey, W. H., et al. (2008) · Brain · doi:10.1093/brain/awn288 · Cited by 175
Self-citationRetractedCraft, S. (2012) · Archives of Neurology · doi:10.1001/archneurol.2011.233 · Cited by 1,253
Intranasal delivery to the central nervous system: Mechanisms and experimental considerations
Dhuria, S. V., Hanson, L. R., & Frey, W. H. (2010) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.21924 · Cited by 1,239
Self-citationInsulin receptors are widely distributed in the central nervous system of the rat
Havránková, J., Roth, J., & Brownstein, M. (1978) · Nature · doi:10.1038/272827a0 · Cited by 1,116
Thorne, R. G., Pronk, G. J., Padmanabhan, V., & Frey, W. H. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.05.029 · Cited by 958
Self-citationThe source of cerebral insulin
Banks, W. A. (2004) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2004.02.040 · Cited by 489
UNGER, J., Livingston, J. H., & Moss, A. (1991) · Progress in Neurobiology · doi:10.1016/0301-0082(91)90015-s · Cited by 399
Quantitative analysis of the olfactory pathway for drug delivery to the brain
Thorne, R. G., Emory, C. R., Ala, T. A., & Frey, W. H. (1995) · Brain Research · doi:10.1016/0006-8993(95)00637-6 · Cited by 352
Self-citationBroadwell, R. D., & Balin, B. J. (1985) · The Journal of Comparative Neurology · doi:10.1002/cne.902420410 · Cited by 181
Li, Y., Field, P. M., & Raisman, G. (2005) · Glia · doi:10.1002/glia.20241 · Cited by 168
Research works printed but not linked: 3
- Frey, 1997, Method of Administering Neurologic Agents to the Brain
- Frey, 2001, Method for Administering Insulin to the Brain
- Frey, 1991, Neurologic Agents for Nasal Administration to the Brain
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Items 101–116 of 116
Sandri, B. J., Ennis-Czerniak, K. M., Kanajam, P., Frey, W. H., Lock, E. F., & Rao, R. (2023) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00311.2022 · Cited by 1
Self-citationIntranasal Delivery of Drugs to the Central Nervous System
Crowe, T. P., & Hsu, W. H. (2024) · AAPS introductions in the pharmaceutical sciences · doi:10.1007/978-3-031-62604-3_6 · Cited by 1
Increased Brain Glutathione Levels by Intranasal Insulin Administration
Kawashima, T., Bhadhprasit, W., Matsumura, N., Kinoshita, C., & Aoyama, K. (2025) · Current Issues in Molecular Biology · doi:10.3390/cimb47040284 · Cited by 1
“Insulin, in Insulin, in particular, can be transferred to the CNS, including the hippocampus, through intranasal administration, in fl uencing related signaling pathways [11]. particular, can be transferred including the hippocampus, through intranasal administration, influencing pathways [11].”
Von der Nase ins Gehirn: Effekte intranasal verabreichten Insulins
Brünner, Y. F., Benedict, C., & Freiherr, J. (2013) · Der Nervenarzt · Cited by 1
da Costa, K. V. T., Carnaúba, A. T. L., Rocha, K. W., de Andrade, K. C. L., & Menezes, P. D. L. (2020) · doi:10.21203/rs.3.rs-39175/v1 · Cited by 1
“The mechanism of intranasal insulin is quite clear, as the olfactory bulb is the largest place for the transformation of intranasal insulin to the brain [35].”
Ocitocina, um “medicamento” ainda em potencial terapêutico para distúrbios psiquiátricos
de Deus, D. M. V., & de Freitas, P. S. (2017) · REVISTA HUM@NAE
Exploring the Link Between Olfaction and Cognition
Bell, G. A. (2014)
Insulin and Brain Injury: Memory, Metabolism and Microglia
Brabazon, F. (2016)
Potential Targeting Sites to the Brain Through Nasal Passage
Govender, M., Indermun, S., Kumar, P., & Choonara, Y. E. (2023) · Springer eBooks · doi:10.1007/978-3-031-23112-4_6
Effect of Intranasal Insulin on Cognitive Function in Diabetic Patients
Ding, Q., Shi, L., Xia, J., Wang, N., & Gao, W. (2024) · Journal of Contemporary Medical Practice · doi:10.53469/jcmp.2024.06(12).04
Elucidating bioadhesive processes in nasal drug delivery systems
Armstrong, M. (2014) · UPT. Syiah Kuala University Library (Syiah Kuala University) · doi:10.48730/6nbf-yx94
Intranasal Delivery of Natural Compounds: A Promising approach for Parkinson’s Disease therapy
Jadhav, P. D., Velhal, A. B., Redasani, V. K., & Rathod, S. T. (2026) · Asian Journal of Pharmaceutical Research · doi:10.52711/2231-5691.2026.00002
Nose-to-Brain Delivery of Biologicals
Torres, J., Correia, A. C., & Silva, A. C. (2025) · Springer handbooks · doi:10.1007/978-3-032-01636-2_8
Luo, P., Zeng, J., Wu, Y., Chen, Y., Gong, G., Huang, Q., & Luo, X. (2026) · BMJ Open · doi:10.1136/bmjopen-2026-122401
“17 Moreover, owing to its low systemic bioavailability (approximately 3–8% relative to intravenous injection), intranasal insulin carries a minimal risk of inducing hypoglycaemia.”
Kim, Y. B., Yun, C.-O., & Yoon, A. R. (2026) · Drug Delivery · doi:10.1080/10717544.2026.2738285
“Within this olfactory axis, transport mechanistically diverges into two distinct intraneuronal and extraneuronal pathways (Thorne et al. 2004; Renner et al. 2012; Drath et al. 2025).”
Qing, D. (2026) · Advances in Clinical Medicine · doi:10.12677/acm.2026.16103382
Metadata
- 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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