Drug delivery across the blood-brain barrier with focused ultrasound and microbubbles

Abstract

Medical treatment options for central nervous system (CNS) diseases are limited due to the inability of most therapeutic agents to penetrate the blood-brain barrier (BBB). Neuropeptides, proteins, and chemotherapeutic agents are notable examples of potential therapeutics where the intact BBB is the major obstacle to their use. Indeed, all large-molecule products of biotechnology such as monoclonal antibodies, recombinant proteins, antisense, or gene therapeutics do not cross the BBB. Although a variety of approaches have been investigated to open the BBB for facilitation of drug delivery, none has achieved clinical applicability. Recent studies suggest that ultrasound in combination with microbubbles might be useful for delivery of drugs to the brain region through transient opening of the BBB. This technique offers a unique noninvasive avenue to deliver a wide range of drugs to the brain and promises to provide treatments for CNS disorders with the advantage of being able to target specific brain regions without unnecessary drug exposure. Clearly, if this method could be applied for different drugs, new CNS therapeutic strategies could emerge at an accelerated pace that is not currently possible in the field of drug discovery and development. This chapter will review both the merits and possible harmful bioeffects of this new approach. It will assessmethods used to verify disruption of the BBB with MRI and examine the results of studies aimed at elucidating the mechanisms of opening the BBB with ultrasound and microbubbles. Moreover, possible interactions of this novel delivery method with brain disease as well as safety aspects of BBB disruption with ultrasound and microbubbles will be addressed.