title: A new brain drug delivery strategy: focused ultrasound-enhanced intranasal drug delivery.
abstract: Central nervous system (CNS) diseases are difficult to treat because of the blood-brain barrier (BBB), which prevents most drugs from entering into the brain. Intranasal (i.n.) administration is a promising approach for drug delivery to the brain, bypassing the BBB; however, its application has been restricted to particularly potent substances and it does not offer localized delivery to specific brain sites. Focused ultrasound (FUS) in combination with microbubbles can deliver drugs to the brain at targeted locations. The present study proposed to combine these two different platform techniques (FUS+i.n.) for enhancing the delivery efficiency of intranasally administered drugs at a targeted location. After i.n. administration of 40 kDa fluorescently-labeled dextran as the model drug, FUS targeted at one region within the caudate putamen of mouse brains was applied in the presence of systemically administered microbubbles. To compare with the conventional FUS technique, in which intravenous (i.v.) drug injection is employed, FUS was also applied after i.v. injection of the same amount of dextran in another group of mice. Dextran delivery outcomes were evaluated using fluorescence imaging of brain slices. The results showed that FUS+i.n. enhanced drug delivery within the targeted region compared with that achieved by i.n. only. Despite the fact that the i.n. route has limited drug absorption across the nasal mucosa, the delivery efficiency of FUS+i.n. was not significantly different from that of FUS+i.v.. As a new drug delivery platform, the FUS+i.n. technique is potentially useful for treating CNS diseases.
authors.affiliation: Department of Biomedical Engineering, Columbia University, New York, New York, United States of America.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Biomedical Engineering, Columbia University, New York, New York, United States of America.
authors.forename: Cherry C
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Department of Biomedical Engineering, Columbia University, New York, New York, United States of America.
authors.forename: Camilo
authors.initials: C
authors.lastname: Acosta
authors.affiliation: Department of Biomedical Engineering, Columbia University, New York, New York, United States of America.
authors.forename: Shih-Ying
authors.initials: SY
authors.lastname: Wu
authors.affiliation: Department of Biomedical Engineering, Columbia University, New York, New York, United States of America.
authors.forename: Tao
authors.initials: T
authors.lastname: Sun
authors.affiliation: Department of Biomedical Engineering, Columbia University, New York, New York, United States of America; Department of Radiology, Columbia University, New York, New York, United States of America.
authors.forename: Elisa E
authors.initials: EE
authors.lastname: Konofagou
mesh_terms: D000281:Administration, Intranasal / Q000379:methods*; D000818:Animals; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging* / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D003911:Dextrans / Q000008:administration & dosage; D016503:Drug Delivery Systems / Q000379:methods*; D008297:Male; D051379:Mice; D045423:Microbubbles; D013010:Sonication; D018084:Ultrasonography, Interventional / Q000379:methods*
chemical_list: D003911:Dextrans