Ultrasound advice

Researchers use ultrasound to poke holes in cells; method could be used for drug delivery.

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ATLANTA—Using a method more commonly applied to visualizing babies in utero or crushing kid­ney stones, Dr. Mark Prausnitz and colleagues at Georgia Institute for Technology and Emory University poked holes in cell membranes as a way to introduce small compounds or macromolecules into various tissue samples. They published their results in a recent issue of Ultrasound in Medicine & Biology.
"There is a need for improved therapy to be able to target drugs in the body, to have them access specific tissues or specific cells, and also the need in some cases to enhance the penetration of a compound of interest into tis­sues or cells within the body," Prausnitz says. "Now, there's a pretty good body of evidence in the literature to show that ultra­sound can open up cells, open up tissues, and make them more permeable to different kinds of molecules, including drugs and DNA."
The Atlanta scientists used a variety of microscopy techniques to monitor the impact of the cav­itation produced by ultrasound as it literally punched holes into the membranes surrounding various cell types. They then watched as the natural repair mechanisms of the cells plugged the holes, allowing the cells to remain viable, but not before the cells took up fluorescently tagged macromolecules like pro­teins and dextrans.
From the therapeutics deliv­ery perspective, Prausnitz sees this nonspecific uptake mechanism that can be harnessed, non- or minimally invasively, to introduce drugs or other molecules to specific organs, tissues or cells.
"There's a quite well-developed technology base for designing ultrasound systems to focus ultra­sound at particular locations in the body—primarily in the context of diagnostic purposes," he explains. "There's a good means to focus that ultrasound with at least centimeter and maybe millimeter resolution, almost anywhere in the body.
"So if the goal is to deliver the drug, for example, just to a tumor, or to deliver DNA just to a certain region, you can then place one or more transducers on the surface and focus that energy at the loca­tion of interest."
Prausnitz's group has focused its attention largely on the applica­tion of ultrasound to ex vivo tis­sues, but he is quick to point to an expanding body of work being done with ultrasound as an in vivo drug delivery vehicle.
"There are probably a dozen or so companies that have using ultra­sound for therapeutic purposes as their primary technology," he says. "But these are mostly start-ups or small publicly traded companies."
"The big companies out there, to my knowledge, don't have signifi­cant programs in this area—com­panies like the drug delivery com­panies as well as the big diagnostic ultrasound companies—but they are monitoring this field and per­haps when the time is right, they will choose to enter also."

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