Investigation of the ability of gas-filled nanobubbles to deliver drug-mimics to the brain via disruption of the blood brain barrier

In this study, we investigate the use of two different nanobubble (NBs) compositions – Span 20 NBs and DMPC NBs - as blood brain barrier (BBB)-opening catalysts and as vectors for drug-delivery into the brain. Studies were undertaken in wild-type mice and NBs or SonoVue microbubbles (MBs) were injected via the tail vein. BBB opening was confirmed by the presence of Evans Blue (EB) dye on the brain sections of euthanized mice after co-injection with either Span 20 NBs or SonoVue MBs and insonation using a 3.5MHz transducer at -2.1MPa peak negative pressure. The degree of BBB opening, assessed by the spread of EB dye, was not significantly different between Span 20 NBs and SonoVue MBs, but further studies suggested that MBs may have the potential to hold open the BBB for a longer period of time than Span 20 NBs. Finally, it was shown that using calcein-loaded Span 20NBs and DMPC NBs that calcein-loaded Span 20 NBs delivered significantly (P<0.05) more calcein to the brain highlighting the potential of NBs as brain delivery vectors.