Thursday, 27 February 2020


Micro- and nanobubbles: a versatile platform for biomedical applications
Application of Contrast Enhancement Ultra Sound (CEUS) started in the late 1960s and it took more than 20 years to develop the first stable, commercially available Ultrasound Contrast Agent (UCA), Albunex®, an albumin-coated and air-filled microsphere.
Microbubbles (MBs) are spherical core–shell gas-filled vesicles, applied as UCAs. The shell acts as a barrier between the encapsulated gas and the surrounding aqueous media, preventing gas dissipation. Several shells with different features can be obtained according to the selected components, such as lipids, proteins and polymers. MBs are normally divided in soft- and hard-shell bubbles. Even though the included gas is responsible for the majority of the bubbles’ acoustic properties, the shell adds a mechanical stiffness and reduces the compressibility of the gas. Therefore, the shell material provides multiple possibilities to tailor the MBs to their specific application by changing visco-elastic properties. Nonetheless, the choice of gas is a factor that has to be considered and different gas can be used to fill the bubble core, such as perfluorocarbons, sulphur hexafluoride, air and carbon dioxide.
Nanobubbles (NBs), bubbles with sizes in the nanometer order of magnitude, have also been developed with the aim of obtaining more efficient systems. Their small sizes allow the possibility of extravasation from blood vessels into the surrounding tissues and ultrasound-targeted site-specific release with minimal invasiveness.
MB and NB undergo volumetric oscillations or acoustic cavitation when insonified by ultrasound and, most importantly, they are able to resonate at diagnostic frequencies. It is due to this behavior that they are currently used as ultrasound contrast agents.
Nowadays their use in therapeutics is under investigation and this is related to their potential to be ‘activated’ in the presence of ultrasound and mediate the delivery of active molecules to specific cell, tissue or organ targets.
A broad variety of materials and sizes generates the basis for multiple and/or combined diagnostic and therapeutic applications. In particular, the combination of UCAs for diagnostics and therapy in one single administration holds a great potential for the future and might be a valuable tool for treatment of several diseases.
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