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 1 um(3) payload volume per each microbubble-liposome particle was achieved, when 100 nm 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, 100 ms, 7 MPa 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.
Klibanov
Alexander L
AL
Cardiovascular Division, Department of Medicine, University of Virginia, Charlottesville VA, 22908 USA. Electronic address: alk6n@virginia.edu.
Shevchenko
Talent I
TI
Cardiovascular Division, Department of Medicine, University of Virginia, Charlottesville VA, 22908 USA.
Raju
Balasundar I
BI
Philips Research North America, Briarcliff Manor NY, 10510 USA.
Seip
Ralf
R
Philips Research North America, Briarcliff Manor NY, 10510 USA.
Chin
Chien T
CT
Philips Research North America, Briarcliff Manor NY, 10510 USA.
D000818:Animals; D004285:Dogs; D016503:Drug Delivery Systems / Q000379:methods*; D005452:Fluoresceins / Q000008:administration & dosage / Q000737:chemistry; D005453:Fluorescence; D008081:Liposomes; D045423:Microbubbles; D013917:Thrombin / Q000008:administration & dosage / Q000737:chemistry; D014465:Ultrasonics
D005452:Fluoresceins; D008081:Liposomes; D013917:Thrombin; C007740:fluorexon