(512c) Development of “Bulky” Lipid Microbubbles for Ultrasound Triggered Drug Delivery

Gas-filled microbubbles have frequently been used as ultrasound contrast agents for imaging and diagnostic applications. More recent applications of microbubble contrast agents have focused on utilizing them as carriers for drugs and nucleic acids. The unique ability of microbubbles to oscillate, and even resonate, during application of ultrasound energy makes them particularly attractive for targeted drug delivery applications. In this study, we developed a novel method of modifying the surface topography of lipid based microbubbles in order to enhance their functionality as drug and gene delivery carriers. By applying hydrostatic pressure to the lipid microbubbles, the mean size of the gas core was reduced and the excess lipid formed folds or lipid protrusions on the surface creating ?bulky? lipid microbubbles. In order to characterize the microbubbles size distribution and surface topography, we utilize several methods including size analysis by light obfuscation, volume displacement, flow cytometry, and fluorescence microscopy. The excess lipid was shed during application of ultrasound energy, which caused microbubbles to rapidly oscillate and pinch off the collapse phase. This mechanism can potentially be used to enhance the ability of microbubbles to release surface-bound drugs for targeted therapeutic applications. This method has important implications in developing next generation microbubbles which are more efficient for ultrasound triggered drug delivery applications.