Theranostics 2017; 7(1):23-30. doi:10.7150/thno.16577

Research Paper

Efficient Enhancement of Blood-Brain Barrier Permeability Using Acoustic Cluster Therapy (ACT)

Andreas K.O. Åslund1✉, Sofie Snipstad1, Andrew Healey2, Svein Kvåle2, Sverre H. Torp3,4, Per C. Sontum2, Catharina de Lange Davies1, Annemieke van Wamel1

1. Department of Physics, Norwegian University of Science and Technology (NTNU), Trondheim, Norway;
2. Phoenix Solutions AS, Oslo, Norway;
3. Department of Pathology and Medical Genetics, St. Olavs University Hospital, Trondheim, Norway;
4. Department of Laboratory Medicine, Children's and Women's Health, NTNU, Trondheim, Norway.

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.

Keywords: Blood-brain barrier opening, focused ultrasound, acoustic cluster therapy (ACT), enhanced drug delivery

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How to cite this article:
Åslund AKO, Snipstad S, Healey A, Kvåle S, Torp SH, Sontum PC, Davies CdL, van Wamel A. Efficient Enhancement of Blood-Brain Barrier Permeability Using Acoustic Cluster Therapy (ACT). Theranostics 2017; 7(1):23-30. doi:10.7150/thno.16577. Available from http://www.thno.org/v07p0023.htm