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Focused Ultrasound Preconditioning for Augmented Nanoparticle Penetration and Efficacy in the Central Nervous System.
Mead, Brian P; Curley, Colleen T; Kim, Namho; Negron, Karina; Garrison, William J; Song, Ji; Rao, Divya; Miller, G Wilson; Mandell, James W; Purow, Benjamin W; Suk, Jung Soo; Hanes, Justin; Price, Richard J.
Afiliação
  • Mead BP; Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, 22908, USA.
  • Curley CT; Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, 22908, USA.
  • Kim N; Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.
  • Negron K; Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.
  • Garrison WJ; Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, 22908, USA.
  • Song J; Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, 22908, USA.
  • Rao D; Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.
  • Miller GW; Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, 22908, USA.
  • Mandell JW; Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA, 22908, USA.
  • Purow BW; Department of Pathology, University of Virginia, Charlottesville, VA, 22908, USA.
  • Suk JS; Department of Neurology, University of Virginia, Charlottesville, VA, 22908, USA.
  • Hanes J; Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.
  • Price RJ; Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.
Small ; 15(49): e1903460, 2019 12.
Article em En | MEDLINE | ID: mdl-31642183
ABSTRACT
Microbubble activation with focused ultrasound (FUS) facilitates the noninvasive and spatially-targeted delivery of systemically administered therapeutics across the blood-brain barrier (BBB). FUS also augments the penetration of nanoscale therapeutics through brain tissue; however, this secondary effect has not been leveraged. Here, 1 MHz FUS sequences that increase the volume of transfected brain tissue after convection-enhanced delivery of gene-vector "brain-penetrating" nanoparticles were first identified. Next, FUS preconditioning is applied prior to trans-BBB nanoparticle delivery, yielding up to a fivefold increase in subsequent transgene expression. Magnetic resonance imaging (MRI) analyses of tissue temperature and Ktrans confirm that augmented transfection occurs through modulation of parenchymal tissue with FUS. FUS preconditioning represents a simple and effective strategy for markedly improving the efficacy of gene vector nanoparticles in the central nervous system.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Sistemas de Liberação de Medicamentos / Nanopartículas / Ondas Ultrassônicas Limite: Animals Idioma: En Revista: Small Assunto da revista: ENGENHARIA BIOMEDICA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Sistemas de Liberação de Medicamentos / Nanopartículas / Ondas Ultrassônicas Limite: Animals Idioma: En Revista: Small Assunto da revista: ENGENHARIA BIOMEDICA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos