From the Department of Biomedical Engineering and the Cardiovascular
Division, University of Virginia, Charlottesville, Va.
Correspondence to Richard J. Price, PhD, Department of Biomedical Engineering, University of Virginia, Box 377, Health Sciences Center, Charlottesville, VA 22908. E-mail rprice{at}virginia.edu
Background—We have previously
shown that the application of ultrasound to thin-shelled microbubbles
flowing through small microvessels (<7 µm in diameter) produces
vessel wall ruptures in vivo. Because many intravascular drug- and
gene-delivery vehicles are limited by the endothelial
barrier, we hypothesized that this phenomenon could be used to deliver
drug-bearing vehicles to tissue.
Methods and Results—An exteriorized rat spinotrapezius muscle
preparation was used. Intravascular fluorescent red blood cells
and polymer microspheres (PM) (205 and 503 nm in diameter) were
delivered to the interstitium of rat skeletal muscle through
microvessel ruptures created by insonifying microbubbles in vivo. On
intravital microscopy, mean dispersion areas per rupture for red blood
cells, 503-nm PM, and 205-nm PM were 14.5x103
µm2, 24.2x103 µm2, and
27.2x103 µm2, respectively. PM
dispersion areas were significantly larger than the mean dispersion
area for red blood cells (P<0.05).
Conclusions—Microvessel ruptures caused by insonification of
microbubbles in vivo may provide a minimally invasive means for
delivering colloidal particles and engineered red blood cells across
the endothelial lining of a targeted tissue region.
© 1998 American Heart Association, Inc.
Brief Rapid Communications
Delivery of Colloidal Particles and Red Blood Cells to Tissue Through Microvessel Ruptures Created by Targeted Microbubble Destruction With Ultrasound
Key Words: ultrasonics • blood cells • microspheres • drug delivery systems • microcirculation
This article has been cited by other articles:
 |
|
 |
|
  S. T. Laing and D. D. McPherson Cardiovascular therapeutic uses of targeted ultrasound contrast agents Cardiovasc Res, September 1, 2009; 83(4): 626 - 635. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kaul and K. Wei When you have eliminated the impossible, whatever remains, however improbable, must be the truth Eur J Echocardiogr, August 1, 2009; 10(6): 713 - 715. [Full Text] [PDF]
|
|
|
|
 |
|
 F. S. Villanueva Ultrasound Mediated Destruction of DNA-Loaded Microbubbles for Enhancement of Cell-Based Therapies: New Promise Amidst a Confluence of Uncertainties? J. Am. Coll. Cardiol. Img., July 1, 2009; 2(7): 880 - 882. [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Stratmeyer, J. F. Greenleaf, D. Dalecki, and K. A. Salvesen Fetal Ultrasound: Mechanical Effects J. Ultrasound Med., April 1, 2008; 27(4): 597 - 605. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. Miller, M. A. Averkiou, A. A. Brayman, E. C. Everbach, C. K. Holland, J. H. Wible Jr, and J. Wu Bioeffects Considerations for Diagnostic Ultrasound Contrast Agents J. Ultrasound Med., April 1, 2008; 27(4): 611 - 632. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Li, Z. Wang, H. Ran, X. Li, Q. Yuan, Y. Zheng, J. Ren, L. Su, W. Zhang, Q. Li, et al. Experimental Research on Therapeutic Angiogenesis Induced by Hepatocyte Growth Factor Directed by Ultrasound-Targeted Microbubble Destruction in Rats J. Ultrasound Med., March 1, 2008; 27(3): 453 - 460. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. J. Dubinsky, C. Cuevas, M. K. Dighe, O. Kolokythas, and J. H. Hwang High-Intensity Focused Ultrasound: Current Potential and Oncologic Applications Am. J. Roentgenol., January 1, 2008; 190(1): 191 - 199. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Stieger, C. F. Caskey, R. H. Adamson, S. Qin, F.-R. E. Curry, E. R. Wisner, and K. W. Ferrara Enhancement of Vascular Permeability with Low-Frequency Contrast-enhanced Ultrasound in the Chorioallantoic Membrane Model Radiology, April 1, 2007; 243(1): 112 - 121. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Atri New Technologies and Directed Agents for Applications of Cancer Imaging J. Clin. Oncol., July 10, 2006; 24(20): 3299 - 3308. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. V. Shohet and P. A. Grayburn Potential Bioeffects of Ultrasonic Destruction of Microbubble Contrast Agents J. Am. Coll. Cardiol., April 4, 2006; 47(7): 1469 - 1470. [Full Text] [PDF]
|
|
|
|
 |
|
 S Enomoto, M Yoshiyama, T Omura, R Matsumoto, T Kusuyama, D Nishiya, Y Izumi, K Akioka, H Iwao, K Takeuchi, et al. Microbubble destruction with ultrasound augments neovascularisation by bone marrow cell transplantation in rat hind limb ischaemia Heart, April 1, 2006; 92(4): 515 - 520. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Vancraeynest, X. Havaux, A.-C. Pouleur, A. Pasquet, B. Gerber, C. Beauloye, P. Rafter, L. Bertrand, and J.-L. J. Vanoverschelde Myocardial delivery of colloid nanoparticles using ultrasound-targeted microbubble destruction Eur. Heart J., January 2, 2006; 27(2): 237 - 245. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Imada, T. Tatsumi, Y. Mori, T. Nishiue, M. Yoshida, H. Masaki, M. Okigaki, H. Kojima, Y. Nozawa, Y. Nishiwaki, et al. Targeted Delivery of Bone Marrow Mononuclear Cells by Ultrasound Destruction of Microbubbles Induces Both Angiogenesis and Arteriogenesis Response Arterioscler Thromb Vasc Biol, October 1, 2005; 25(10): 2128 - 2134. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Chapman, J. Windle, F. Xie, A. McGrain, and T. R. Porter Incidence of Cardiac Arrhythmias With Therapeutic Versus Diagnostic Ultrasound and Intravenous Microbubbles J. Ultrasound Med., August 1, 2005; 24(8): 1099 - 1107. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Cosyns, C. Weytjens, M. Vanderhoogstrate, C. Daniels, D. Schoors, and G. Van Camp Tissue Doppler imaging does not show infraclinical alteration of myocardial function after contrast echocardiography Eur J Echocardiogr, August 1, 2005; 6(4): 238 - 242. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Abramowicz Ultrasonographic Contrast Media: Has the Time Come in Obstetrics and Gynecology? J. Ultrasound Med., April 1, 2005; 24(4): 517 - 531. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Bekeredjian, P. A. Grayburn, and R. V. Shohet Use of ultrasound contrast agents for gene or drug delivery in cardiovascular medicine J. Am. Coll. Cardiol., February 1, 2005; 45(3): 329 - 335. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Song, P. S. Cottler, A. L. Klibanov, S. Kaul, and R. J. Price Microvascular remodeling and accelerated hyperemia blood flow restoration in arterially occluded skeletal muscle exposed to ultrasonic microbubble destruction Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2754 - H2761. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Kondo, K. Ohmori, A. Oshita, H. Takeuchi, S. Fuke, K. Shinomiya, T. Noma, T. Namba, and M. Kohno Treatment of acute myocardial infarction by hepatocyte growth factor gene transfer: The first demonstration of myocardial transfer of a "functional" gene using ultrasonic microbubble destruction J. Am. Coll. Cardiol., August 4, 2004; 44(3): 644 - 653. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P.A Dijkmans, L.J.M Juffermans, R.J.P Musters, A van Wamel, F.J ten Cate, W van Gilst, C.A Visser, N de Jong, and O Kamp Microbubbles and ultrasound: from diagnosis to therapy Eur J Echocardiogr, August 1, 2004; 5(4): 245 - 246. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Li, K. Tachibana, M. Kuroki, and M. Kuroki Gene Transfer with Echo-enhanced Contrast Agents: Comparison between Albunex, Optison, and Levovist in Mice--Initial Results Radiology, November 1, 2003; 229(2): 423 - 428. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-R. Orden, J. S. Jurvelin, and P. P. Kirkinen Kinetics of a US Contrast Agent in Benign and Malignant Adnexal Tumors Radiology, February 1, 2003; 226(2): 405 - 410. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Beeri, J. L. Guerrero, G. Supple, S. Sullivan, R. A. Levine, and R. J. Hajjar New Efficient Catheter-Based System for Myocardial Gene Delivery Circulation, October 1, 2002; 106(14): 1756 - 1759. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Song, M. Qi, S. Kaul, and R. J. Price Stimulation of Arteriogenesis in Skeletal Muscle by Microbubble Destruction With Ultrasound Circulation, September 17, 2002; 106(12): 1550 - 1555. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Price and S. Kaul Contrast Ultrasound Targeted Drug and Gene Delivery: An Update on a New Therapeutic Modality Journal of Cardiovascular Pharmacology and Therapeutics, September 1, 2002; 7(3): 171 - 180. [Abstract] [PDF]
|
|
|
|
|
|
J. Song, J. C. Chappell, M. Qi, E. J. VanGieson, S. Kaul, and R. J. Price Influence of injection site, microvascular pressureand ultrasound variables on microbubble-mediated delivery of microspheres to muscle J. Am. Coll. Cardiol., February 20, 2002; 39(4): 726 - 731. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Ay, X. Havaux, G. Van Camp, B. Campanelli, G. Gisellu, A. Pasquet, J.-F. Denef, J. A. Melin, and J.-L. J. Vanoverschelde Destruction of Contrast Microbubbles by Ultrasound: Effects on Myocardial Function, Coronary Perfusion Pressure, and Microvascular Integrity Circulation, July 24, 2001; 104(4): 461 - 466. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J K Blomley, J. C Cooke, E. C Unger, M. J Monaghan, and D. O Cosgrove Science, medicine, and the future: Microbubble contrast agents: a new era in ultrasound BMJ, May 19, 2001; 322(7296): 1222 - 1225. [Full Text]
|
|
|
|
 |
|
 D. L. Miller and J. Quddus Diagnostic ultrasound activation of contrast agent gas bodies induces capillary rupture in mice PNAS, August 17, 2000; (2000) 180294397. [Abstract] [Full Text]
|
|
|
|
|
|
R. V. Shohet, S. Chen, Y.-T. Zhou, Z. Wang, R. S. Meidell, R. H. Unger, and P. A. Grayburn Echocardiographic Destruction of Albumin Microbubbles Directs Gene Delivery to the Myocardium Circulation, June 6, 2000; 101(22): 2554 - 2556. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Mukherjee, J. Wong, B. Griffin, S. G. Ellis, T. Porter, S. Sen, and J. D. Thomas Ten-fold augmentation of endothelial uptake of vascular endothelial growth factor with ultrasound after systemic administration J. Am. Coll. Cardiol., May 1, 2000; 35(6): 1678 - 1686. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. Miller and J. Quddus Diagnostic ultrasound activation of contrast agent gas bodies induces capillary rupture in mice PNAS, August 29, 2000; 97(18): 10179 - 10184. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Teupe, S. Richter, B. Fisslthaler, V. Randriamboavonjy, C. Ihling, I. Fleming, R. Busse, A. M. Zeiher, and S. Dimmeler Vascular Gene Transfer of Phosphomimetic Endothelial Nitric Oxide Synthase (S1177D) Using Ultrasound-Enhanced Destruction of Plasmid-Loaded Microbubbles Improves Vasoreactivity Circulation, March 5, 2002; 105(9): 1104 - 1109. [Abstract] [Full Text] [PDF]
|
|