The DOI matches its Crossref record; 114 of the 117 references it cites were found in a registry or an index.
Mechanism of intranasal drug delivery directly to the brain
Abstract
Neurological diseases are becoming increasingly prominent worldwide due to rapidly aging populations, which greatly contributes to increasing healthcare costs. The development of neuroprotective drugs has so far proven exceptionally difficult due to the blood-brain barrier. One novel approach to address this challenge is to administer drugs intranasally to noninvasively bypass the blood-brain barrier. The intranasal route can thus transport drugs directly to the brain from the nasal cavity along the olfactory and trigeminal nerves. The purpose of this review is to describe the details of this mechanism to better direct future research. The intranasal route is composed of two pathways, one being intracellular while the other being extracellular. The intracellular pathway begins with endocytosis by olfactory sensory cells, followed by axonal transport to their synaptic clefts in the olfactory bulb where the drug is exocytosed. This transynaptic process is repeated by olfactory neurons, thereby distributing the drug to other brain regions. In the extracellular mechanism, drugs are transported directly into the cerebral spinal fluid by first passing through the paracellular space across the nasal epithelium, then through the perineural space to the subarachnoid space of the brain. With a growing body of evidence and trials in both rodent and human models, this is an exciting area for research as therapeutics come to market.
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“The intra-neuronal transport of neuropeptides from the nasal cavity to the olfactory bulb takes several hours, 29 which makes it more likely that IN administered peptides are primarily transported along extra-neuronal routes (ie, through intercellular clefts of the olfactory epithelium).”
From Intranasal insulin (2021) · cites this paper as [33]
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3 of the 117 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
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Evaluation of intranasal delivery route of drug administration for brain targeting
Erdő, F., Bors, L. A., Farkas, D., Bajza, Á., & Gizurarson, S. S. (2018) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2018.10.009 · Cited by 773
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Intranasal drug delivery: opportunities and toxicologic challenges during drug development
Keller, L.-A., Merkel, O. M., & Popp, A. (2021) · Drug Delivery and Translational Research · doi:10.1007/s13346-020-00891-5 · Cited by 636
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Metadata
- Authors
- Crowe, T. P., Greenlee, M. H. W., Kanthasamy, A. G., & Hsu, W. H.
- Affiliations
- Iowa State University (US)
- Corresponding author
- Hsu, Walter H.
- Venue
- Life Sciences
- Publisher
- Elsevier BV
- Published
- 2018-02
- Volume
- 195
- Pages
- 44-52
- ISSN
- 0024-3205 (ISSN-L)
- OpenAlex
- W2776146933
- Cited by
- 721
- References
- 117
- Citations by year
- 2026: 97 · 2025: 123 · 2024: 100 · 2023: 92 · 2022: 91 · 2021: 82 · 2020: 72 · 2019: 49 · 2018: 15
- FWCI
- 3.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Life Sciences (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Surgery › Head and Neck Surgical Oncology
- Keywords
- intranasal drug delivery, blood-brain barrier bypass, olfactory pathway, trigeminal pathway, olfactory sensory neurons, axonal transport, olfactory bulb, paracellular transport, perineural space, subarachnoid space, cerebrospinal fluid, neuroprotective agents, neurological disorders
- MeSH terms
- Administration, Intranasal, Animals, Blood-Brain Barrier, Brain, Humans, Nasal Cavity, Nervous System Diseases, Drug Delivery Systems
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