Ultrasound unlocks the gates of drug delivery

Ultrasound could one day play a key role in drug delivery, if researchers can harness the cavitation effect produced by ultrasound beams that allows drugs to pass through the protective membranes of cells.

Cavitation in the ultrasound field causes a shock-wave effect, said Mark Prausnitz, a professor of chemical and biomolecular engineering at the Georgia Institute of Technology. Fluid movement associated with this phenomenon opens holes in the cell membranes, which allow entry of foreign molecules into the cells. The cells then respond to the creation of the holes by mobilizing intracellular vesicles to patch the holes within minutes.

The technique could find future use in systemic therapy in oncology, particularly for large-molecule drugs that cannot easily move through cell membranes, according to results of a study published by Prausnitz and colleagues in Ultrasound in Medicine and Biology.

The research team employed five microscopy techniques in living prostate cancer and animal cells. They confirmed that the powerful cavitation effect produces enough force to stimulate cell membrane permeability. The holes close down quickly, but allow the entry of therapeutic molecules that are 50 nanometers in diameter, larger than most compounds used for gene therapy (J Ultras Med Bio. 2006:32[6]915-924).

One of the benefits of ultrasound is that it is noninvasive. Physicians could apply chemotherapy locally or throughout the body, then focus the ultrasound beam only on areas where tumors exist. That would increase the cell permeability and drug uptake only in the targeted cells and avoid affecting healthy cells elsewhere, Prausnitz said.

Investigators also focused on the mechanism of membrane permeability recovery. This could help determine the proper window of opportunity for drug delivery. The team used prostate cancer cells in the study, but they have also studied other types of cells with good results.

There are caveats and challenges ahead for the technique, however. In the study, ultrasound cavitation did not produce consistent results across the entire volume of cells, with only about one-third affected. Researchers also need to properly establish ultrasound bioeffects to optimize power in regards to safety concerns. In addition, ultrasound has no FDA approval for drug delivery applications.

Researchers need to learn how to control exposure before physicians can use ultrasound for therapy in the body. They also must devise a system that provides enough impact to allow transport into the cell, but not so much of an impact that the cell would be stressed beyond its ability to repair the injury, Praunitz said.

"One of the real challenges is going to be translating the successes that have occurred in the laboratory and in small animals into clinical success in people," said Prausnitz. "Now that we better understand the mechanism of ultrasound's effects, we can more effectively take advantage of it for medical therapy."

The research was supported by the National Institutes of Health and the National Science Foundation.

For more information from the Diagnostic Imaging archives:

Imaging offers insight into blood-brain barrier permeability

Interventional oncology seeks role within radiology

Company sees ultrasound as potential clot buster