CoChat
Sign Up
Cited by 721Advanced Drug Delivery SystemsBarrier Structure and Function StudiesHead and Neck Surgical Oncology

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

Crowe, Tyler P., Greenlee, M. Heather West, Kanthasamy, Anumantha G., Hsu, Walter H.·2018·Life Sciences
DOI 10.1016/j.lfs.2017.12.025
Open this paper in CoChat — free account

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.

Overview

Integrity signals

Registry

Crossref · 10.1016/j.lfs.2017.12.025

Cites

114 of 114 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

Flagged first, then by citations

Show all 117 references

3 of the 117 references couldn’t be matched to a known paper.

Research works printed but not linked: 2

  1. Schwalbe, 1869, Die arachnoidalraum, ein lymphraum und sein zusammenhang mit den perichorioidalraum, Zentralbl. Med. Wiss., 7, 465
  2. Kim, 2009, Gene knockout in the olfactory bulb, amygdala, and hypothalamus by intranasal siRNA administration, Kor. J. Anat., 42, 285

Cited by

Sorted by citations

Items 501–600 of 721

Related

See all

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.
ORCID
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review