Methods of preparing targeted microbubble shells

Lead Inventors: Mark Borden, Ph.D.; Cherry ChenProblem or Unmet Need:A microbubble is a gaseous colloidal particle with diameter less than 10 um, of which the surface comprises amphiphilic phospholipids self-assembled to form a lipid monolayer shell. Due to the compressible gas core, microbubbles provide a sensitive acoustic response. They serve as echo contrast agents for ultrasound imaging, as drug delivery vehicles for targeted therapy, and as gas carriers for blood oxygenation. Designing and engineering non-immunogenic, ultrasound-triggered microbubbles for targeting is critical to expand the utility and scope of these applications. This invention presents a new way of fabricating a buried-ligand architecture (BLA) where the microbubble surface was coated with a bimodal poly(ethylene glycol) (PEG) brush following microbubble fabrication, purification and size selection. It has been shown, for the first time, streptavidin-induced surface structure formation, leading to escess surface area that may be useful to enhanding ligand-receptor mediated adhesion for targeting applications. This invention demonstrates the feasibility of post-labeling for smallmolecule ligands to BLA microbubbles to generate stealth targeted ultrasound contrast agents.

Specifically makes microbubbles shells with the buried ligand architecture Uses avidin/biotin biding to create excess surface area on the microbubbles Provides a means of quantifying the percentage of microbubbles with surface structures Safety, economy, ease of manufacture, quality of product, quality of performance

Ultrasound molecular imaging Imaging with other modalities Targeted drug delivery Targeted gene delivery Targeted gas delivery Targeted therapy

This invention presents a new way of fabricating a buried-ligand architecture (BLA) where the microbubble surface was coated with a bimodal poly(ethylene glycol) (PEG) brush following microbubble fabrication, purification and size selection. It...

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