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Drug delivery across the blood brain barrier

Virginie Papadopoulou

 

In addition to their use in imaging, ultrasound contrast agents offer a unique method enhancing the delivery of therapeutic drugs to targeted sites while providing real-time image-guided feedback of the process. In numerous biomedical therapy applications, potent drugs are associated with severe systemic side-effects as their administration through blood vessels distributes them in healthy tissue in addition to just the therapeutic site of interest. As such, ways to enhance the uptake of the drug directly in the target site are a major biomedical research target, in particular to better treat cancer. In addition, some sites such as the brain are extremely difficult to deliver drugs to. To protect the brain from potentially fatal infections, the vascular network in that region is structured in a way that prevents most blood components from entering, and has secondary active transport mechanisms that return any objects that manage to get out back into blood stream.

Ultrasound contrast agents are a blood pool marker as they normally stay confined to the blood vessels were they are injected and circulate. Interestingly, their behavior under ultrasound can be modified so that, at a specific site of interest, they exert appropriate mechanical effects on, and flow circulation around, vessel boundaries. This in turn can be used to transiently and locally increase the amount of drugs that can be delivered through boundaries (such as vessels or tight epithelial layers) and in cells. In our lab, we are investigating both the fundamental mechanisms (pharmacoengineering collaboration with Dr Zaharoff’s laboratory at NC State) and blood-brain barrier delivery potential of this technique with numerous applications including Alzheimer’s and Glioblastoma therapy (collaborations with Prof. Konofagou’s laboratory at Columbia University and with Dr Brudno at NC State).