Characterizing ultrasound-controlled drug release by high-speed fluorescence imaging

Ultrasound contrast agents (UCAs) microbubbles (MBs) can be preloaded with a therapeutic agents to achieve high efficiency for US-triggered drug delivery. Here we use fluorescence labeling as a substitute for theraputic drug, and use ultra high-speed fluorescence imaging for time-resolved observation of the drug release. Two configurations of drug delivery vehicles were investigated - I) lipid-shelled (unloaded) MBs and II) liposome-loaded (loaded) MBs. Different release phenomena were observed. The dynamics of release was found to be strongly dependent on ultrasonic parameters and on the MB´s shell properties. MBs shrinkage following US exposure was analyzed and it indicated close correlation with the fluorescence release. This study provides valuable insights into the drug release mechanisms for ultrasound-controlled drug delivery.