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Emerging Engineering Technologies for Opening the BBB

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Drug Delivery to the Brain

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 10))

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Abstract

Current treatments of neurological and neurodegenerative diseases are limited due to the lack of a truly noninvasive, transient, and regionally selective brain drug delivery method. The brain is particularly difficult to deliver drugs to because of the blood–brain barrier (BBB). The impermeability of the BBB is due to the tight junctions between adjacent endothelial cells and highly regulatory transport systems of the endothelial cell membranes. The main function of the BBB is ion and volume regulation to ensure the conditions necessary for proper synaptic and axonal signaling. However, the same permeability properties that keep the brain healthy also present tremendous obstacles to its pharmacological treatment. Until a solution to the trans-BBB delivery problem is found, treatments of neurological diseases will remain impeded. Over the past decade, methods that combine focused ultrasound (FUS) and microbubbles have been shown to offer the unique capability to noninvasively, locally, and transiently open the BBB. Four of the main challenges to the application of FUS are (1) to assess its safety profile, (2) to unveil the mechanism by which the BBB opens and closes, (3) to control and predict the opened BBB properties and duration of the opening, and (4) to assess its promise for brain drug delivery. In this chapter, we discuss all of these challenges, along with findings in both small (mice) and large (nonhuman primates) animals, and emphasize the clinical potential for this technique.

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Acknowledgements

The work shown here was performed by Yao-Sheng Tung, James Choi, Thomas Deffieux, Babak Baseri, Fabrice Marquet, and Fotios Vlachos, previously with the Ultrasound and Elasticity Imaging Laboratory of the Biomedical Engineering Department at Columbia. Collaborators on the microbubble studies were Jameel Feshitan and Mark Borden (currently at the University of Colorado-Boulder) and on the non-human primate studies were Tobias Techert and Vincent Ferrera (Columbia University). The research was supported by NIH R01 EB009041, NIH R21 EY018505, NSF CAREER 064471, the Kinetics Foundation and the Kavli Institute.

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Authors and Affiliations

  1. Department of Biomedical Engineering, Columbia University, 351 Engineering Terrace, 1210 Amsterdam Avenue, New York, NY, 10027, USA

    Elisa E. Konofagou

  2. Department of Radiology, Columbia University, New York, NY, USA

    Elisa E. Konofagou

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  1. Elisa E. Konofagou
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Correspondence to Elisa E. Konofagou .

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Editors and Affiliations

  1. Pharmaceutical Biosciences, Uppsala University Pharmacokinetics and Drug Therapy, Uppsala, Sweden

    Margareta Hammarlund-Udenaes

  2. LACDR/Pharmacology, Leiden University, Leiden, The Netherlands

    Elizabeth C.M. de Lange

  3. Pharmaceutical Sciences Division, University of Wisconsin-Madison School of Pharmacy, Madison, Wisconsin, USA

    Robert G. Thorne

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Konofagou, E.E. (2014). Emerging Engineering Technologies for Opening the BBB. In: Hammarlund-Udenaes, M., de Lange, E., Thorne, R. (eds) Drug Delivery to the Brain. AAPS Advances in the Pharmaceutical Sciences Series, vol 10. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-9105-7_20

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