title: Cardiovascular drug delivery with ultrasound and microbubbles.
abstract: Microbubbles lower the threshold for cavitation of ultrasound and have multiple potential therapeutic applications in the cardiovascular system. One of the first therapeutic applications to enter into clinical trials has been microbubble-enhanced sonothrombolysis. Trials were conducted in acute ischemic stroke and clinical trials are currently underway for sonothrombolysis in treatment of acute myocardial infarction. Microbubbles can be targeted to epitopes expressed on endothelial cells and thrombi by incorporating targeting ligands onto the surface of the microbubbles. Targeted microbubbles have applications as molecular imaging contrast agents and also for drug and gene delivery. A number of groups have shown that ultrasound with microbubbles can be used for gene delivery yielding robust gene expression in the target tissue. Work has progressed to primate studies showing delivery of therapeutic genes to generate islet cells in the pancreas to potentially cure diabetes. Microbubbles also hold potential as oxygen therapeutics and have shown promising results as a neuroprotectant in an ischemic stroke model. Regulatory considerations impact the successful clinical development of therapeutic applications of microbubbles with ultrasound. This paper briefly reviews the field and suggests avenues for further development.
authors: Depts. of Radiology and Biomedical Engineering, The University of Arizona Health Sciences Center, Tucson, AZ, USA. Electronic address: eunger@radiology.arizona.edu.
authors: Evan
authors: E
authors: Unger
authors: Dept. of Cardiology, University of Nebraska Medical Center, Omaha, NE, USA.
authors: Thomas
authors: T
authors: Porter
authors: Division of Cardiovascular Medicine, Oregon Health & Science University, Portland, OR, USA.
authors: Jonathan
authors: J
authors: Lindner
authors: Baylor Heart and Vascular Center, Dallas, TX, USA.
authors: Paul
authors: P
authors: Grayburn
mesh_terms: D000818:Animals; D002317:Cardiovascular Agents / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D005466:Fluorocarbons / Q000008:administration & dosage; D018014:Gene Transfer Techniques; D006801:Humans; D061185:Mechanical Thrombolysis; D045423:Microbubbles; D010100:Oxygen / Q000008:administration & dosage; D014465:Ultrasonics / Q000379:methods*; D010420:Pentanes
chemical_list: D002317:Cardiovascular Agents; D005466:Fluorocarbons; D010100:Oxygen; C008806:perfluoropentane; D010420:Pentanes
keywords: Cardiovascular; Drug delivery; Fluorocarbons; Gene delivery; Microbubbles; Oxygen delivery; Perfluorobutane; Perfluoropentane; Perfluoropropane; Sonothrombolysis; Ultrasound