Ultrasound-triggered release of materials entrapped in microbubble–liposome constructs: A tool for targeted drug delivery

We investigated the preparation of ultrasound-triggered drug delivery system, based on a pendant complex of microbubble coated with liposomes. Biotinylated decafluorobutane microbubbles were coated with biotinylated liposomes via a streptavidin linker. Liposomes were prepared incorporating calcein and thrombin. Based on initial concentration of calcein, over 1um3 payload volume per each microbubble–liposome particle was achieved, when 100nm liposomes were used. Insonation of microbubble–liposome pendants in vitro resulted in the complete destruction of microbubbles and triggered release of a significant fraction of the entrapped material. Treatment with 1MHz ultrasound (5 pulses, 100ms, 7MPa peak negative acoustic pressure) resulted in the release of ~30% of entrapped calcein, as estimated by the fluorescence quenching assay. Thrombin release from liposomes complexed with microbubbles (11% of entrapped material) due to ultrasound treatment was estimated by a chromogenic substrate study. Prior to insonation, substrate hydrolysis was at background level. Ultrasound-triggered release of thrombin from the pendant complexes caused an acceleration of blood clotting. In vitro insonation by 1MHz ultrasound (5 100ms pulses at 7MPa) resulted in the release of entrapped calcein and thrombin from the liposome–microbubble pendant complexes. [Display omitted]