The use of microbubbles to target drug delivery

The recent advances in gene therapy and molecular biology have improved the interest in methods of noninvasive delivery of therapeutic agents. Besides the well known application of microbubbles as contrast agents for diagnostic ultrasound, microbubbles have also been demonstrated an effective technique for targeted delivery of drugs and genes [1-6]. Drugs can be incorporated into the microbubbles in a number of different ways, including binding of the drug to the microbubble shell and attachment of site-specific ligands. As perfluorocarbon-filled microbubbles are sufficiently stable for circulating in the vasculature as blood pool agents, they act as carriers of these agents until the site of interest is reached. Ultrasound applied over the skin surface can then be used to burst the microbubbles at this site, causing localized release of the drug [7-10]. This technique then permits using lower concentrations of drugs systemically, and concentration of the drug only where it is needed. This improved therapeutic index may be extremely advantageous in cases of drugs with hazardous systemic side effects, like cytotoxic agents. Albumin-encapsulated microbubbles have also demonstrated to adhere to the vessel walls in the setting of endothelial dysfunction [11]. This also may be a method of targeting delivery with microbubbles but without the application of ultrasound.Two possible strategies for delivering drugs and genes with microbubbles are emerging. The first consists on the ultrasound-mediated microbubble destruction, which is based on the cavitation of microbubbles induced by ultrasound application, and the second is the direct delivery of substances bound to microbubbles in the absence of ultrasound. Different drugs and genes can be incorporated into the ultrasound contrast agents. It has already been demonstrated that perfluorocarbon-filled albumin microbubbles avidly bind proteins and synthetic oligonucleotides [12]. In a similar way, microbubbles can directly tak