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Augmentation of cardiac protein delivery using ultrasound targeted microbubble destruction.

Bekeredjian R, Chen S, Grayburn PA, Shohet RV

Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, NB 11.200, Dallas, TX 75390-8573, USA.

Gas-filled microbubbles have become an important tool as ultrasonic contrast agents. We have previously shown that ultrasound-targeted microbubble destruction (UTMD) can direct plasmids to the heart. The aim of this study was to evaluate UTMD for protein delivery. Six different groups of rats received 1 microg of luciferase protein with varying protocols: (1) luciferase-loaded microbubbles and ultrasound; (2) luciferase only; (3) luciferase and ultrasound; (4) luciferase-loaded microbubbles; (5) unloaded microbubbles incubated with luciferase and ultrasound; (6) unloaded microbubbles with ultrasound followed by luciferase. Relative luminescence units per mg protein per s were determined in hearts and control organs. The rats that received ultrasound and luciferase-loaded bubbles showed a six-fold higher cardiac luciferase uptake compared with control groups that did not include bubbles. None of the other groups significantly augmented cardiac luciferase activity. We conclude that ultrasound-targeted microbubble destruction can substantially and noninvasively augment organ-specific delivery of proteins.

Published 3 May 2005 in Ultrasound Med Biol, 31(5): 687-91.
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