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Bubble liposomes (BLs), which are gas-encapsulated liposomes several hundred nanometers in diameter, are expected to be developed as a novel tool for gene and drug delivery using ultrasound acoustic radiation force. However, since BLs are several hundred nanometers in diameter, difficulties exist in controlling their behaviors in blood flow under ultrasound exposure, since acoustic radiation forces have less effect on these small bubbles. In this study, we investigated the feasibility of active control of BLs in an artificial blood vessel under ultrasound exposure and attempted to evaluate the controllability. Then, we investigated the appropriate ultrasound conditions for active path selection of BLs in a bifurcated flow by applying acoustic radiation force. We prepared a single transducer to orient BLs toward one desired path. Two other transducers were targeted at the two paths after the bifurcation. We evaluated the areas of trapped BLs in the two paths after the bifurcation, to determine which path had increased BLs. The result showed a significant increase in area of trapped BLs in the desired path compared to the other path. Then, we defined the induction index of BLs by evaluating the area of trapped BLs, and changed the ultrasound conditions for active path selection of BLs by varying the sound pressure and frequency. We found that more BLs could be oriented to a desired path at higher sound pressure. For further study, we are aiming at active control of BLs in vivo.

Evaluation of Active Control of Bubble Liposomes in a Bifurcated Flow under Various Ultrasound Conditions