Drug Delivery Vehicles
Focused ultrasound can be used to release encapsulated therapeutics (e.g. genes, chemotherapeutics), delivering them in high concentrations to a precise point while minimizing their systemic effects.
In this process, a therapeutic is encapsulated in or bonded to a carrier vehicle (e.g. microbubble, liposome), that is sensitive to either elevated temperatures or pressures. These carrier vehicles are then injected into the bloodstream. This encapsulation prevents the therapeutic 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 therapeutic or to decouple from the therapeutic which is then quickly absorbed by the surrounding tissue. Although the encapsulated therapeutic is present throughout the entire body, it is only released in the area targeted by focused ultrasound. In this way, the therapeutic can circulate harmlessly throughout the body, and only be activated where desired.
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 therapeutics from microbubbles (i.e. ultrasound contrast agents) can be readily monitored in real time using ultrasound imaging. If therapeutics 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. As LTSLs pass through the hyperthermic region, the increased temperature causes their decomposition and the subsequent release of encapsulated therapeutics. For acoustic pressure-sensitive carriers, ultrasound induced cavitation and radiation forces can “pop open” the carrier or decouple the therapeutics from the carriers, allowing for their release in the targeted area.
The delivery of ultrasound-inert therapeutic carriers can also be enhanced using focused ultrasound. Hyperthermia, stable cavitation, and radiation forces from focused ultrasound have all been shown to increase local therapeutic absorption from the bloodstream. In heated tissue, blood flow and the rate of chemical diffusion are both enhanced, leading to more efficient uptake of therapeutics into the surrounding tissue. Stable cavitation induces acoustic streaming and increases cell membrane permeability, which also locally increases therapeutic bioavailability.
Clinically, combining focused ultrasound with therapeutic delivery vehicles presents an attractive method for delivery of cancer therapeutics. These therapeutics, which are typically delivered systemically, are very toxic to healthy cells. By taking advantage of therapeutic delivery vehicles, cancer therapeutics 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.
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