Acoustic fragmentation of therapeutic contrast agents designed for localized drug delivery

The current methods for delivery of lipid-soluble chemotherapeutic agents may be improved using acoustically active lipospheres (AALs). These microbubbles are designed to release a drug payload when disrupted with acoustic energy at the desired site. Delivery at localized areas would decrease the systemic side effects and increase uptake at the desired site. The drug delivery agents we are examining are provided by ImaRx Pharmaceuticals, and consist of an outer lipid shell with an inner oil layer of triacetin and a gas core. These AALs are 0.5-8 /spl mu/m in diameter when activated, with an oil shell from 0.3-1.0 /spl mu/m in thickness. The large volume of the oil shell allows these drug delivery vehicles to carry a large payload of hydrophobic drugs compared to nano-scale drug delivery systems. For these AALs, the observed destruction mechanism varies with the resting radius, with agents smaller than resonance size undergoing a symmetric collapse and producing a set of small equal-sized fragments. Between resonance size and twice resonance size, surface waves become visible, and the oscillations become asymmetrical. For agents greater than twice the resonance radius, the destruction mechanism changes to a pinch-off, with one fragment containing a large fraction of the original volume.