Sonoporation: Concept and Mechanisms.

Contrast agents for ultrasound are now routinely used for diagnosis and imaging. In recent years, new promising possibilities for targeted drug delivery have been proposed that can be realized by using the microbubble composing ultrasound contrast agents (UCAs). The microbubbles can carry drugs and selectively adhere to specific sites in the human body. This capability, in combination with the effect known as sonoporation, provides great possibilities for localized drug delivery. Sonoporation is a process in which ultrasonically activated UCAs, pulsating nearby biological barriers (cell membrane or endothelial layer), increase their permeability and thereby enhance the extravasation of external substances. In this way drugs and genes can be delivered inside individual cells without serious consequences for the cell viability. Sonoporation has been validated both in-vitro using cell cultures and in-vivo in preclinical studies. However, today, the mechanisms by which molecules cross the biological barriers remain unrevealed despite a number of proposed theories. This chapter will provide a survey of the current studies on various hypotheses regarding the routes by which drugs are incorporated into cells or across the endothelial layer and possible associated microbubble acoustic phenomena.