A unique method to deliver a bioactive substance to the vascular endothelium uses ultrasound and delivery vehicles engineered to contain both gas and drug payload to localize drug delivery. The vehicles (called acoustically-active lipospheres or AALs) include a lipid shell, an oil layer to carry hydrophobic drugs which is associated with the lipid shell, and a small gas core. AALs are similar to ultrasound contrast agents: they can be non-destructively deflected using ultrasound radiation force, and fragmented with high-intensity ultrasound pulses. An optimized sequence of ultrasound pulses can deflect the AALs towards a vessel wall with radiation force and then disrupt them, painting their contents across the vascular endothelium. The resulting fragments can be anchored to endothelium with molecular targeting ligands that may be incorporated into the shell.