Characterization of novel microbubble contrast agents

An exciting recent development in ultrasound microbubble contrast agent technology is their extension from non-specific diagnostic tools to targeted and therapeutic agents. This involves attachment of targeting, or otherwise active, ligands to the microbubbles. The aim of this work was to evaluate the effect of these additional ingredients on the acoustic properties and stability of microbubbles with shells consisting of either albumin or phospholipids. Non-conjugated bubbles were found to behave comparably to their commercial equivalents. Both albumin and phospholipid bubbles show reduced stability following conjugation. Cross-linking of the albumin shell was found to improve bubble stability. For the lipid bubbles improvement in stability was also recorded upon conjugation via polymeric spacers. This work demonstrates that the acoustic characterisation of novel bubbles is crucial in refining the manufacturing process. The results presented show that conjugation of large molecules into the bubble can affect the acoustic behavior of the bubbles. The approaches employed in this work allow testing of chemical hypotheses in the design of novel targeted agents.