Remote control of the permeability of the blood-brain barrier by magnetic heating of nanoparticles: A proof of concept for brain drug delivery.
Despite advances in neurology, drug delivery to the brain remains a substantial challenge. This is mainly due to the insurmountable and selective nature of the blood-brain barrier (BBB). In this study, we show that the thermal energy generated by magnetic heating (hyperthermia) of commercially available magnetic nanoparticles (MNPs) in the brain capillaries of rats can transiently increase barrier permeability. Here, the fluorescent Evans Blue (EB) dye was used to verify the BBB integrity. Results indicate a substantial but reversible opening of the BBB where hyperthermia is applied. Also, in this investigation, analysis of CD68 immunoreactivity, an indicator of inflammation, implies that this technique is not associated with any inflammation. We have previously investigated theranostic (therapeutic and diagnostic) capabilities of the MNPs, therefore, the findings presented in this investigation are particularly encouraging for a novel targeted drug delivery system to the brain.
Institute of Biomedical Engineering, Polytechnique de Montréal, Montréal, Canada; Department of Pharmacology, Faculty of Medicine, Université de Montréal, Montréal, Canada.
Seyed Nasrollah
SN
Tabatabaei
Department of Pharmacology, Faculty of Medicine, Université de Montréal, Montréal, Canada.
Hélène
H
Girouard
Departement of Pediatrics, Faculty of Medicine, Université de Montréal, Montréal, Canada; Pediatric Hematologist-Oncologist at CHU Sainte-Justine Hospital, Montréal, Canada.
Anne-Sophie
AS
Carret
Institute of Biomedical Engineering, Polytechnique de Montréal, Montréal, Canada; Department of Computer and Software Engineering, Polytechnique de Montréal, Montréal, Canada. Electronic address: sylvain.martel@polymtl.ca.
Sylvain
S
Martel
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000648:ultrastructure; D002199:Capillary Permeability; D016503:Drug Delivery Systems / Q000379:methods*; D005070:Evans Blue / Q000008:administration & dosage*; D006979:Hyperthermia, Induced; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D005070:Evans Blue; D058185:Magnetite Nanoparticles; C067980:CD68 antigen, human; D000097382:CD68 Molecule
Alternating current; Blood–brain barrier; Drug delivery; Hyperthermia; Magnetic nanoparticles