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Evaluating the safety profile of focused ultrasound and microbubble-mediated treatments to increase blood-brain barrier permeability.
Expert Opinion on Drug Delivery 2019 January 11
INTRODUCTION: Treatment of several diseases of the brain are complicated by the presence of the skull and the blood-brain barrier (BBB). Focused ultrasound (FUS) and microbubble (MB)-mediated BBB treatment is a minimally invasive method to transiently increase the permeability of blood vessels in targeted brain areas. It can be used as a general delivery system to increase the concentration of therapeutic agents in the brain parenchyma. Areas covered: Over the past two decades, the safety of using FUS+MBs to deliver agents across the BBB has been interrogated through various methods of imaging, histology, biochemical assays, and behaviour analyses. Here we provide an overview of the factors that affect the safety profile these treatments, describe methods by which FUS+MB treatments are controlled, and discuss data that have informed the assessment of treatment risks. Expert opinion: There remains a need to assess the risks associated with clinically relevant treatment strategies, specifically repeated FUS+MB treatments, with and without therapeutic agent delivery. Additionally, efforts to develop metrics by which FUS+MB treatments can be easily compared across studies would facilitate a more rapid consensus on the risks associated with this intervention.
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