Journal
JOURNAL OF CONTROLLED RELEASE
Volume 148, Issue 1, Pages 13-17Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2010.07.115
Keywords
Microbubbles; Liposomes; Ultrasound; Triggered release; Thrombin; Clotting; Calcein
Funding
- NCI NIH HHS [R33 CA102880, R33 CA102880-03, R33CA102880, R33 CA102880-04, R33 CA102880-05, R33 CA102880-02] Funding Source: Medline
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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 1 MHz ultrasound (5 pulses, 100 ms, 7 MPa peak negative acoustic pressure) resulted in the release of similar to 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. (C) 2010 Published by Elsevier B.V.
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