Glymphatic-assisted perivascular brain delivery of intrathecal small gold nanoparticles

Lilius, Tuomas O.; Mortensen, Kristian Nygaard; Deville, Claire; Lohela, Terhi J.; Stæger, Frederik Filip; Sigurdsson, Björn; Rosenholm, Marko; Beekman, F.J.; Jensen, Andreas I.

doi:10.1016/j.jconrel.2023.01.054

Glymphatic-assisted perivascular brain delivery of intrathecal small gold nanoparticles

Title

Glymphatic-assisted perivascular brain delivery of intrathecal small gold nanoparticles

Author

Lilius, Tuomas O. (University of Copenhagen; University of Helsinki)
Mortensen, Kristian Nygaard (University of Copenhagen)
Deville, Claire (Technical University of Denmark)
Lohela, Terhi J. (Faculty of Health and Medical Sciences; Viikki Biocenter 1)
Stæger, Frederik Filip (University of Copenhagen)
Sigurdsson, Björn (University of Copenhagen)
Rosenholm, Marko (University of Copenhagen; University of Helsinki)
Beekman, F.J. (TU Delft RST/Biomedical Imaging; University Medical Center Utrecht; MILabs B.V.)
Jensen, Andreas I. (Technical University of Denmark)

Date

2023

Abstract

Nanoparticles are ultrafine particulate matter having considerable potential for treatment of central nervous system (CNS) disorders. Despite their tiny size, the blood-brain barrier (BBB) restricts their access to the CNS. Their direct cerebrospinal fluid (CSF) administration bypasses the BBB endothelium, but still fails to give adequate brain uptake. We present a novel approach for efficient CNS delivery of ¹¹¹In-radiolabelled gold nanoparticles (AuNPs; 10–15 nm) via intra-cisterna magna administration, with tracking by SPECT imaging. To accelerate CSF brain influx, we administered AuNPs intracisternally in conjunction with systemic hypertonic saline, which dramatically increased the parenchymal AuNP uptake, especially in deep brain regions. AuNPs entered the CNS along periarterial spaces as visualized by MRI of gadolinium-labelled AuNPs and were cleared from brain within 24 h and excreted through the kidneys. Thus, the glymphatic-assisted perivascular network augment by systemic hypertonic saline is a pathway for highly efficient brain-wide distribution of small AuNPs.

Subject

Central nervous system drug delivery
Glymphatic system
Hypertonic solution
Nanoparticles
Single-photon emission tomography

To reference this document use:

http://resolver.tudelft.nl/uuid:bb44b530-2e22-4948-86ce-44f11830b0cb

DOI

https://doi.org/10.1016/j.jconrel.2023.01.054

ISSN

0168-3659

Source

Journal of Controlled Release: official journal of the Controlled Release Society, 355, 135-148

Part of collection

Institutional Repository