Drug Delivery Vehicles

In this process, a drug is encapsulated in or bonded to a carrier vehicle (e.g. microbubble, liposome), that is sensitive to either elevated temperatures or pressures¹. These carrier vehicles are then injected into the bloodstream. This encapsulation prevents the drug from interacting with its surroundings as it circulates throughout the body. Next, ultrasound is focused on the targeted area, causing the carriers to release the drug or to decouple from the drug which is then quickly absorbed by the surrounding tissue. Although the encapsulated drug is present throughout the entire body, it is only released in the area targeted by focused ultrasound. In this way, the drug can circulate harmlessly throughout the body, and only be activated where desired.^2-5

A significant amount of recent scientific work has been devoted to optimizing the various types of carrier vehicles such as microbubbles, liposomes, and nanoparticles. Release of drugs from microbubbles (i.e. ultrasound contrast agents) can be readily monitored in real time using ultrasound imaging. If drugs are coupled to MRI contrast agents, MRI can also be used for monitoring. With the use of low temperature sensitive liposomes (LTSLs), high intensity focused ultrasound is used to induce mild hyperthermia in a targeted location, characterized by a temperature elevation to approximately 40ºC^3,6. As LTSLs pass through the hyperthermic region, the increased temperature causes their decomposition and the subsequent release of encapsulated drugs^3,5. For acoustic pressure-sensitive carriers, ultrasound induced cavitation and radiation forces can “pop open” the carrier or decouple the drugs from the carriers, allowing for their release in the targeted area⁷.

Hyperthermia⁶, stable cavitation⁸, and radiation forces⁹ from focused ultrasound have all been shown to increase local drug absorption from the bloodstream. In heated tissue, blood flow and the rate of chemical diffusion are both enhanced⁶, leading to more efficient uptake of drugs into the surrounding tissue. Stable cavitation induces acoustic streaming and increases cell membrane permeability⁸, which also locally increases drug bioavailability.

Clinically, combining focused ultrasound with drug delivery vehicles presents an attractive method for chemotherapy delivery. These drugs, which are typically delivered systemically, are very toxic to healthy cells. By taking advantage of drug delivery vehicles, chemotherapeutics can be delivered at high concentrations in the tumor without the systemic toxicities. These vehicles can also be used to deliver genes to specific targets in the brain to treat neurological disorders.