title: Noninvasive Targeted Transcranial Neuromodulation via Focused Ultrasound Gated Drug Release from Nanoemulsions.
abstract: Targeted, noninvasive neuromodulation of the brain of an otherwise awake subject could revolutionize both basic and clinical neuroscience. Toward this goal, we have developed nanoparticles that allow noninvasive uncaging of a neuromodulatory drug, in this case the small molecule anesthetic propofol, upon the application of focused ultrasound. These nanoparticles are composed of biodegradable and biocompatible constituents and are activated using sonication parameters that are readily achievable by current clinical transcranial focused ultrasound systems. These particles are potent enough that their activation can silence seizures in an acute rat seizure model. Notably, there is no evidence of brain parenchymal damage or blood-brain barrier opening with their use. Further development of these particles promises noninvasive, focal, and image-guided clinical neuromodulation along a variety of pharmacological axes.
authors.affiliation: Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine , Baltimore, Maryland 21231, United States.|Department of Biomedical Engineering and the Translational Tissue Engineering Center, Johns Hopkins University School of Medicine , Baltimore, Maryland 21231, United States.|Department of Radiology, Stanford University , Stanford, California 94305, United States.
authors.forename: Raag D
authors.identifier: 0000-0001-5259-5606
authors.initials: RD
authors.lastname: Airan
authors.affiliation: Department of Biomedical Engineering and the Translational Tissue Engineering Center, Johns Hopkins University School of Medicine , Baltimore, Maryland 21231, United States.|Institute for NanoBioTechnology, Johns Hopkins University , Baltimore, Maryland 21231, United States.
authors.forename: Randall A
authors.initials: RA
authors.lastname: Meyer
authors.affiliation: Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine , Baltimore, Maryland 21231, United States.
authors.forename: Nicholas P K
authors.initials: NP
authors.lastname: Ellens
authors.affiliation: Department of Biomedical Engineering and the Translational Tissue Engineering Center, Johns Hopkins University School of Medicine , Baltimore, Maryland 21231, United States.
authors.forename: Kelly R
authors.initials: KR
authors.lastname: Rhodes
authors.affiliation: Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine , Baltimore, Maryland 21231, United States.|National Cancer Institute/National Institutes of Health , Bethesda, Maryland 20892, United States.
authors.forename: Keyvan
authors.initials: K
authors.lastname: Farahani
authors.affiliation: Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine , Baltimore, Maryland 21231, United States.|Institute for NanoBioTechnology, Johns Hopkins University , Baltimore, Maryland 21231, United States.|Department of Oncology, Johns Hopkins University School of Medicine , Baltimore, Maryland 21231, United States.
authors.forename: Martin G
authors.identifier: 0000-0001-6753-3010
authors.initials: MG
authors.lastname: Pomper
authors.affiliation: Neuroscience Laboratory, Hugo Moser Research Institute, Kennedy Krieger Institute , Baltimore, Maryland 21287, United States.|Department of Neurology, Johns Hopkins Medical Institutions , Baltimore, Maryland 21287, United States.
authors.forename: Shilpa D
authors.identifier: 0000-0001-5136-9594
authors.initials: SD
authors.lastname: Kadam
authors.affiliation: Department of Biomedical Engineering and the Translational Tissue Engineering Center, Johns Hopkins University School of Medicine , Baltimore, Maryland 21231, United States.|Institute for NanoBioTechnology, Johns Hopkins University , Baltimore, Maryland 21231, United States.|Department of Oncology, Johns Hopkins University School of Medicine , Baltimore, Maryland 21231, United States.|Departments of Neurosurgery, Ophthalmology, and Materials Science and Engineering, Johns Hopkins University School of Medicine , Baltimore, Maryland 21231, United States.
authors.forename: Jordan J
authors.identifier: 0000-0003-4176-3808
authors.initials: JJ
authors.lastname: Green
mesh_terms: D000777:Anesthetics / Q000008:administration & dosage / Q000737:chemistry; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004337:Drug Carriers; D065546:Drug Liberation; D004655:Emulsions / Q000737:chemistry*; D005466:Fluorocarbons / Q000737:chemistry; D008279:Magnetic Resonance Imaging; D053758:Nanoparticles / Q000737:chemistry*; D018377:Neurotransmitter Agents / Q000008:administration & dosage* / Q000737:chemistry; D061848:Optical Imaging; D015742:Propofol / Q000008:administration & dosage / Q000737:chemistry; D051381:Rats; D012640:Seizures / Q000188:drug therapy; D014018:Tissue Distribution; D000069453:Ultrasonic Waves
chemical_list: D000777:Anesthetics; D004337:Drug Carriers; D004655:Emulsions; D005466:Fluorocarbons; D018377:Neurotransmitter Agents; D015742:Propofol
keywords: Neuromodulation; focused ultrasound; gated drug release; nanoparticles