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Mechanism of intranasal drug delivery directly to the brain

Crowe, Tyler P., Greenlee, M. Heather West, Kanthasamy, Anumantha G., Hsu, Walter H.·2018·Life Sciences

DOI 10.1016/j.lfs.2017.12.025

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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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Authors: Crowe, T. P., Greenlee, M. H. W., Kanthasamy, A. G., & Hsu, W. H.
Affiliations: Iowa State University (US)
Corresponding author: Hsu, Walter H.
ORCID: Crowe, Tyler P.
Greenlee, M. Heather West
Kanthasamy, Anumantha G.
Hsu, Walter H.
Venue: Life Sciences
Publisher: Elsevier BV
Published: 2018-02
Volume: 195
Pages: 44-52
ISSN: 0024-3205 (ISSN-L)
DOI: 10.1016/j.lfs.2017.12.025
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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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Mechanism of intranasal drug delivery directly to the brain

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