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Cited by 83Nanoparticle-Based Drug DeliveryAdvanced Drug Delivery SystemsCerebrospinal fluid and hydrocephalus

Fate of nanoparticles in the central nervous system after intrathecal injection in healthy mice

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Householder, K. T., Dharmaraj, S., Sandberg, D. I., Wechsler-Reya, R. J., Sirianni, R. W.·2019·Scientific Reports
DOI 10.1038/s41598-019-49028-wPMC PMC6715675
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Abstract

Cerebrospinal fluid (CSF) is produced in the cerebral ventricles and circulates within the subarachnoid space (SAS) of the brain and spinal cord, where it exchanges with interstitial fluid of the parenchyma. The access of CSF to the entire central nervous system (CNS) makes it an attractive medium for drug delivery. However, few intrathecal (IT) therapies have reached the clinic due, in part, to limited distribution and rapid clearance. Given the success of nanoparticle (NP) carriers in prolonging circulation and improving delivery of systemically administered agents, we sought to evaluate the distribution of IT injected NPs within the CNS. We administered fluorescent, 100 nm PEGylated-NPs into the cisterna magna of healthy mice and studied their distribution along the brain and spinal cord. Our data demonstrate that NPs are capable of distributing rapidly through the SAS along the entire neuraxis with reproducible, anatomically defined patterns of delivery. NPs were well retained within the leptomeninges for over 3 weeks, showing preference for ventral surfaces and minimal penetration into the CNS parenchyma. Clearance of NPs occurred across the cribriform plate into the nasal mucosa, with a small fraction of NPs localizing with nerve roots exiting the spinal column. Larger 10 µm particles were also capable of moving through the SAS but did not achieve as widespread distribution. These studies demonstrate the ability of NPs to achieve widespread delivery along the neuraxis and highlight IT administration as a potentially significant route of administration for delivery of nanomedicine to the subarachnoid space.

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  • CSF reaches the entire CNS by exchanging with the interstitial fluid of the CNS parenchyma.

    “By exchanging with the interstitial fluid of the CNS’s parenchyma, CSF reaches the entire CNS, making it an effective route for drug delivery.”

    From Lipid Nanoparticles Enhance mRNA Delivery to the Central Nervous System Upon Intrathecal Injection (2025) · cites this paper as [21]

    The Discussion (page not provided) says CSF moves around the brain and down the spinal cord, supporting its broad access to the CNS. The non-abstract passages do not establish the claimed exchange with parenchymal interstitial fluid as the means by which it reaches the entire CNS. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

  • Intrathecal injection provides direct access to the cerebrospinal fluid (CSF).

    “It provides direct access to the cerebrospinal fluid (CSF), which is generated in the brain ventricles and flows through the subarachnoid space (SAS) surrounding the brain and spinal cord.[21]”

    From Lipid Nanoparticles Enhance mRNA Delivery to the Central Nervous System Upon Intrathecal Injection (2025) · cites this paper as [21]

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Cited by

Sorted by citations

Authors
Householder, K. T., Dharmaraj, S., Sandberg, D. I., Wechsler-Reya, R. J., & Sirianni, R. W.
Affiliations
  • Barrow Neurological Institute (US)
  • The University of Texas Health Science Center at Houston (US)
Corresponding author
Sirianni, R. W.
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2019-08-29
Volume
9
Issue
1
Pages
12587-12587
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-019-49028-w
PMC
PMC6715675
OpenAlex
W2970205776
Cited by
83
References
7
Citations by year
2026: 14 · 2025: 10 · 2024: 11 · 2023: 8 · 2022: 11 · 2021: 18 · 2020: 11
FWCI
2.83
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Barrow Neurological Foundation
  • Ian's Friends Foundation
  • National Institutes of Health
  • National Institute of Neurological Disorders and Stroke (R01NS111292)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD099543)
Topics
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
Keywords
intrathecal administration, nanoparticles, central nervous system, subarachnoid space, cerebrospinal fluid, PEGylated nanoparticles, nanoparticle distribution, leptomeninges, cribriform plate, nasal mucosa, spinal cord, brain, nanomedicine delivery, particle size effects, fluorescent nanoparticles
MeSH terms
Animals, Brain, Injections, Spinal, Polyethylene Glycols, Polystyrenes, Spinal Cord, Mice, Nanoparticles

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