title: Efficient Enhancement of Blood-Brain Barrier Permeability Using Acoustic Cluster Therapy (ACT).
abstract: The blood-brain barrier (BBB) is a major obstacle in drug delivery for diseases of the brain, and today there is no standardized route to surpass it. One technique to locally and transiently disrupt the BBB, is focused ultrasound in combination with gas-filled microbubbles. However, the microbubbles used are typically developed for ultrasound imaging, not BBB disruption. Here we describe efficient opening of the BBB using the promising novel Acoustic Cluster Therapy (ACT), that recently has been used in combination with Abraxane® to successfully treat subcutaneous tumors of human prostate adenocarcinoma in mice. ACT is based on the conjugation of microbubbles to liquid oil microdroplets through electrostatic interactions. Upon activation in an ultrasound field, the microdroplet phase transfers to form a larger bubble that transiently lodges in the microvasculature. Further insonation induces volume oscillations of the activated bubble, which in turn induce biomechanical effects that increase the permeability of the BBB. ACT was able to safely and temporarily permeabilize the BBB, using an acoustic power 5-10 times lower than applied for conventional microbubbles, and successfully deliver small and large molecules into the brain.
authors.affiliation: Department of Physics, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
authors.forename: Andreas K O
authors.initials: AK
authors.lastname: Åslund
authors.affiliation: Department of Physics, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
authors.forename: Sofie
authors.initials: S
authors.lastname: Snipstad
authors.affiliation: Phoenix Solutions AS, Oslo, Norway.
authors.forename: Andrew
authors.initials: A
authors.lastname: Healey
authors.affiliation: Phoenix Solutions AS, Oslo, Norway.
authors.forename: Svein
authors.initials: S
authors.lastname: Kvåle
authors.affiliation: Department of Pathology and Medical Genetics, St. Olavs University Hospital, Trondheim, Norway;; Department of Laboratory Medicine, Children's and Women's Health, NTNU, Trondheim, Norway.
authors.forename: Sverre H
authors.initials: SH
authors.lastname: Torp
authors.affiliation: Phoenix Solutions AS, Oslo, Norway.
authors.forename: Per C
authors.initials: PC
authors.lastname: Sontum
authors.affiliation: Department of Physics, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
authors.forename: Catharina de Lange
authors.initials: CL
authors.lastname: Davies
authors.affiliation: Department of Physics, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
authors.forename: Annemieke
authors.initials: A
authors.lastname: van Wamel
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology* / Q000528:radiation effects*; D016503:Drug Delivery Systems / Q000379:methods*; D051379:Mice; D045423:Microbubbles; D009821:Oils; D010539:Permeability / Q000528:radiation effects*; D013010:Sonication / Q000379:methods*; D000069453:Ultrasonic Waves
chemical_list: D009821:Oils
keywords: Blood-brain barrier opening; acoustic cluster therapy (ACT); enhanced drug delivery; focused ultrasound