Ultrasonic delivery of a chemotherapeutic agent using acoustic droplet vaporization (ADV)

The ability to localize, both spatially and temporally, a chemotherapeutic agent could be used to reduce the systemic toxicity associated with conventional chemotherapy regimens. Ultrasound (US)-triggered drug delivery systems, such as microbubbles or emulsions, present the ability to localize the effect of chemotherapy agents. In the case of phase-shift emulsions, the activation by US results in the production of gas bubbles - a process known as acoustic droplet vaporization (ADV). Here, the ability of ADV to selectively release chlorambucil (CHL), a clinically-used chemotherapeutic agent, from an emulsion is tested in vitro. A micron-sized emulsion, stabilized by bovine serum albumin, was made using perfluoropentane, soybean oil, and CHL. A linear array (6.3 MHz, mechanical index = 0.7) was used to vaporize the CHL-laden emulsion after introduction into chambers containing adherent Chinese hamster ovary (CHO) cells. An 84.3±3.8% growth inhibition was observed with ultrasound, compared to 46.7±7.6% growth inhibition without ultrasound. Therefore, ADV has the potential to localize the release of an agent encapsulated within the triggered emulsion.