Print Email Facebook Twitter 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 deliveryGlymphatic systemHypertonic solutionNanoparticlesSingle-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 Document type journal article Rights © 2023 Tuomas O. Lilius, Kristian Nygaard Mortensen, Claire Deville, Terhi J. Lohela, Frederik Filip Stæger, Björn Sigurdsson, Marko Rosenholm, F.J. Beekman, Andreas I. Jensen, More Authors Files PDF 1_s2.0_S0168365923000639_main.pdf 8.61 MB Close viewer /islandora/object/uuid:bb44b530-2e22-4948-86ce-44f11830b0cb/datastream/OBJ/view