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Ultrasound-mediated delivery and distribution of polymeric nanoparticles in the normal brain parenchyma of a metastatic brain tumour model.
Baghirov, Habib; Snipstad, Sofie; Sulheim, Einar; Berg, Sigrid; Hansen, Rune; Thorsen, Frits; Mørch, Yrr; Davies, Catharina de Lange; Åslund, Andreas K O.
Afiliación
  • Baghirov H; Department of Physics, The Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
  • Snipstad S; Department of Physics, The Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
  • Sulheim E; Department of Physics, The Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
  • Berg S; SINTEF Materials and Chemistry, Trondheim, Norway.
  • Hansen R; SINTEF Medical Technology, Trondheim, Norway.
  • Thorsen F; Department of Circulation and Medical Imaging, The Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
  • Mørch Y; SINTEF Medical Technology, Trondheim, Norway.
  • Davies CL; Department of Circulation and Medical Imaging, The Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
  • Åslund AKO; Molecular Imaging Center and Kristian Gerhard Jebsen Brain Tumour Research Centre, Department of Biomedicine, University of Bergen, Bergen, Norway.
PLoS One ; 13(1): e0191102, 2018.
Article en En | MEDLINE | ID: mdl-29338016
The treatment of brain diseases is hindered by the blood-brain barrier (BBB) preventing most drugs from entering the brain. Focused ultrasound (FUS) with microbubbles can open the BBB safely and reversibly. Systemic drug injection might induce toxicity, but encapsulation into nanoparticles reduces accumulation in normal tissue. Here we used a novel platform based on poly(2-ethyl-butyl cyanoacrylate) nanoparticle-stabilized microbubbles to permeabilize the BBB in a melanoma brain metastasis model. With a dual-frequency ultrasound transducer generating FUS at 1.1 MHz and 7.8 MHz, we opened the BBB using nanoparticle-microbubbles and low-frequency FUS, and applied high-frequency FUS to generate acoustic radiation force and push nanoparticles through the extracellular matrix. Using confocal microscopy and image analysis, we quantified nanoparticle extravasation and distribution in the brain parenchyma. We also evaluated haemorrhage, as well as the expression of P-glycoprotein, a key BBB component. FUS and microbubbles distributed nanoparticles in the brain parenchyma, and the distribution depended on the extent of BBB opening. The results from acoustic radiation force were not conclusive, but in a few animals some effect could be detected. P-glycoprotein was not significantly altered immediately after sonication. In summary, FUS with our nanoparticle-stabilized microbubbles can achieve accumulation and displacement of nanoparticles in the brain parenchyma.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Polímeros / Ultrasonido / Encéfalo / Neoplasias Encefálicas / Modelos Animales de Enfermedad / Nanopartículas / Metástasis de la Neoplasia Límite: Animals / Female / Humans Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2018 Tipo del documento: Article País de afiliación: Noruega Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Polímeros / Ultrasonido / Encéfalo / Neoplasias Encefálicas / Modelos Animales de Enfermedad / Nanopartículas / Metástasis de la Neoplasia Límite: Animals / Female / Humans Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2018 Tipo del documento: Article País de afiliación: Noruega Pais de publicación: Estados Unidos