TY - JOUR
T1 - Glymphatic-assisted perivascular brain delivery of intrathecal small gold nanoparticles
AU - Lilius, Tuomas O.
AU - Mortensen, Kristian Nygaard
AU - Deville, Claire
AU - Lohela, Terhi J.
AU - Stæger, Frederik Filip
AU - Sigurdsson, Björn
AU - Fiordaliso, Elisabetta M.
AU - Rosenholm, Marko
AU - Kamphuis, Chris
AU - Beekman, Freek J.
AU - Jensen, Andreas I.
AU - Nedergaard, Maiken
N1 - Publisher Copyright:
© 2023
PY - 2023/3
Y1 - 2023/3
N2 - 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.
AB - 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.
KW - Central nervous system drug delivery
KW - Glymphatic system
KW - Hypertonic solution
KW - Nanoparticles
KW - Single-photon emission tomography
UR - http://www.scopus.com/inward/record.url?scp=85149775856&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2023.01.054
DO - 10.1016/j.jconrel.2023.01.054
M3 - Article
C2 - 36731802
AN - SCOPUS:85149775856
SN - 0168-3659
VL - 355
SP - 135
EP - 148
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -