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Monocytes as Carriers of Magnetic Nanoparticles for Tracking Inflammation in the Epileptic Rat Brain
Journal article   Peer reviewed

Monocytes as Carriers of Magnetic Nanoparticles for Tracking Inflammation in the Epileptic Rat Brain

Hadas Han, Sara Eyal, Emma Portnoy, Aniv Mann, Miriam Shmuel, Mony Benifla, Dana Ekstein and Boris Polyak
Current drug delivery, v 16(7), pp 637-644
2019
DOI: https://doi.org/10.2174/1567201816666190619122456
PMID: 31237208
Featured in Collection :   UN Sustainable Development Goals @ Drexel

Abstract

Animals Boron Compounds - administration & dosage Disease Models, Animal Drug Delivery Systems Epilepsy, Temporal Lobe - chemically induced Epilepsy, Temporal Lobe - metabolism Fluorescent Dyes - administration & dosage Hippocampus - metabolism Inflammation - metabolism Kidney - metabolism Lithium Chloride Liver - metabolism Magnetite Nanoparticles - administration & dosage Male Monocytes Pilocarpine Rats, Wistar Spleen - metabolism
Inflammation is a hallmark of epileptogenic brain tissue. Previously, we have shown that inflammation in epilepsy can be delineated using systemically-injected fluorescent and magnetite- laden nanoparticles. Suggested mechanisms included distribution of free nanoparticles across a compromised blood-brain barrier or their transfer by monocytes that infiltrate the epileptic brain. In the current study, we evaluated monocytes as vehicles that deliver nanoparticles into the epileptic brain. We also assessed the effect of epilepsy on the systemic distribution of nanoparticleloaded monocytes. The in vitro uptake of 300-nm nanoparticles labeled with magnetite and BODIPY (for optical imaging) was evaluated using rat monocytes and fluorescence detection. For in vivo studies we used the rat lithium-pilocarpine model of temporal lobe epilepsy. In vivo nanoparticle distribution was evaluated using immunohistochemistry. 89% of nanoparticle loading into rat monocytes was accomplished within 8 hours, enabling overnight nanoparticle loading ex vivo. The dose-normalized distribution of nanoparticle-loaded monocytes into the hippocampal CA1 and dentate gyrus of rats with spontaneous seizures was 176-fold and 380-fold higher compared to the free nanoparticles (p<0.05). Seizures were associated with greater nanoparticle accumulation within the liver and the spleen (p<0.05). Nanoparticle-loaded monocytes are attracted to epileptogenic brain tissue and may be used for labeling or targeting it, while significantly reducing the systemic dose of potentially toxic compounds. The effect of seizures on monocyte biodistribution should be further explored to better understand the systemic effects of epilepsy.

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Domestic collaboration
International collaboration
Web of Science research areas
Pharmacology & Pharmacy
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