Passive delivery of liposomes to mouse brain after blood-brain barrier opening induced by focused ultrasound with microbubbles

Focused ultrasound (FUS) combined with microbubbles is an attractive method to deliver therapeutic agents to brain tissue noninvasively, transiently and locally such as antibodies, gene vectors, liposomal drugs. The objective of this study is to investigate passive delivery outcome of liposomes after ultrasound mediated blood-brain barrier (BBB) disruption. Microbubbles were injected intraveneously through mice tail vein at 0.1 μL/g. Focused ultrasound (center frequency: 1.2819 MHz) was applied to mice brains with 10 ms pulse length and 1 Hz repetition frequency at acoustic power 1.1 W for 60 s. After sonication, 55-nm and 120-nm rhodamine-labeled liposomes were administered to mice intraveneously. Fluorescence imaging of brain coronal sections showed that the spatial distribution of delivered liposomes across BBB was characterized by scattered spots and heterogeneous. However, the quantitative analysis results indicated that passive deliveries of liposomes across BBB were confined, especially for 120-nm liposomes.