Ultrasonic gene and drug delivery to the cardiovascular system

Ultrasound targeted microbubble destruction has evolved as a promising tool for organ specific gene and drug delivery. This technique has initially been developed as a method in myocardial contrast echocardiography, destroying intramyocardial microbubbles to characterize refill kinetics. When loading similar microbubbles with a bioactive substance, ultrasonic destruction of microbubbles may release the transported substance in the targeted organ. Furthermore, high amplitude oscillations of microbubbles lead to increased capillary and cell membrane permeability, thus facilitating tissue and cell penetration of the released substance. While this technique has been successfully used in many organs, its application in the cardiovascular system has dominated so far. Drug delivery using microbubbles has played a minor role in the cardiovascular system. In contrast, gene transfer has been successfully achieved in many studies. Both viral and non-viral vectors were used for loading on microbubbles. This review article will give an overview on studies that have applied ultrasound targeted microbubble destruction to deliver substances in the heart and blood vessels. It will show potential therapeutic targets, especially for gene therapy, describe feasible substances that can be loaded on microbubbles, and critically discuss prospects and limitations of this technique.