Methods of preparation of multifunctional microbubbles and their in vitro / in vivo assessment of stability, functional and structural properties.

Microbubbles (MBs) are ultrasound responsive colloidal particles with a strong potential to become theranostic agents, combining the contrast agent activity with therapeutic functionality. In the last decades, MBs have played a significant role as ultrasound contrast agents in diagnostic imaging. MBs have also shown great potential in applications such as molecular imaging, drug delivery, gene therapy and sonothrombolysis. A full understanding of all physical processes underlying the MBs' stability and acoustic behavior is available in the literature. Efforts have been now addressed to the study of chemical and biological features of multifunctional lipid, protein, or polymer shelled MBs. A number of methods of preparation of "smart" MBs for ultrasound image-guided therapy have been recently developed. In this review, different approaches utilized in preparing multifunctional MBs are discussed with specific attention to the current strategies adopted to design MBs with specialized functions. In vitro / in vivo assessment of MBs' stability and activity will be discussed with a particular emphasis on the emerging applications of MBs for the multiple imaging modalities, the effective opening of blood brain barrier, BBB, and for the therapeutic treatment of antimicrobial films.