title: Focused ultrasound-enhanced intranasal brain delivery of brain-derived neurotrophic factor.
abstract: The objective of this study was to unveil the potential mechanism of focused ultrasound (FUS)-enhanced intranasal (IN) brain drug delivery and assess its feasibility in the delivery of therapeutic molecules. Delivery outcomes of fluorescently-labeled dextrans to mouse brains by IN administration either before or after FUS sonication were compared to evaluate whether FUS enhances IN delivery by active pumping or passive diffusion. Fluorescence imaging of brain slices found that IN administration followed by FUS sonication achieved significantly higher delivery than IN administration only, while pre-treatment by FUS sonication followed by IN administration was not significantly different from IN administration only. Brain-derived neurotrophic factor (BDNF), a promising neurotrophic factor for the treatment of many central nervous system diseases, was delivered by IN followed by FUS to demonstrate the feasibility of this technique and compared with the established FUS technique where drugs are injected intravenously. Immunohistochemistry staining of BDNF revealed that FUS-enhanced IN delivery achieved similar locally enhanced delivery as the established FUS technique. This study suggested that FUS enhances IN brain drug delivery by FUS-induced active pumping of the drug and demonstrated that FUS-enhanced IN delivery is a promising technique for noninvasive and localized delivery of therapeutic molecules to the brain.
authors.affiliation: Department of Biomedical Engineering, Columbia University, New York, New York, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Biomedical Engineering, Columbia University, New York, New York, USA.
authors.forename: Georgiana Zong Xin
authors.initials: GZ
authors.lastname: Yang
authors.affiliation: Department of Biomedical Engineering, Columbia University, New York, New York, USA.
authors.forename: Hoheteberhan
authors.initials: H
authors.lastname: Getachew
authors.affiliation: Department of Biomedical Engineering, Columbia University, New York, New York, USA.
authors.forename: Camilo
authors.initials: C
authors.lastname: Acosta
authors.affiliation: Department of Biomedical Engineering, Columbia University, New York, New York, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Sierra Sánchez
authors.affiliation: Department of Biomedical Engineering, Columbia University, New York, New York, USA.|Department of Radiology, Columbia University, New York, New York, USA.
authors.forename: Elisa E
authors.initials: EE
authors.lastname: Konofagou
mesh_terms: D000281:Administration, Intranasal / Q000379:methods; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage*; D003911:Dextrans / Q000008:administration & dosage; D016503:Drug Delivery Systems / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013010:Sonication / Q000379:methods
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D003911:Dextrans