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New method of delivering chemotherapy using ultrasound works in BYU lab

Cancer patients undergoing chemotherapy often endure painful side effects caused by the powerful drugs as they course through their entire bodies, damaging healthy tissue and tumors alike.

Brigham Young University researchers are reporting in the December issue of the prestigious oncology journal "Cancer Research" that they have successfully tested a new method in laboratory animals that would concentrate the impact of cancer drugs on specific cancerous tissues, thus sparing the rest of the body from harm.

Their method combines two, key innovations: packaging a drug in tiny molecules of water-soluble plastic so that the drug would not interact while passing through a person's bloodstream, then using ultrasound to release the drug from its package at the specific part of the body affected by the cancer.

William G. Pitt, professor of chemical engineering at BYU and principal investigator on the project, said he is pleased that the tests produced significant reductions of tumor size in laboratory animals.

"This method shows potential in offering controlled drug delivery, which could reduce the negative side effects that arise during chemotherapy and could localize the treatment at the tumor site," said Pitt, cautioning that human application is still several years away.

Richard H. Wheeler, director of clinical research for the Huntsman Cancer Institute, says Pitt's research is interesting and innovative.

"The use of focused ultrasound to release the packaged drug maximally within tumor tissue holds promise for the cancer patient of increasing the chance for tumor response while reducing side effects," said Wheeler.

The experiments are the product of years of work on ultrasound drug delivery by Pitt combined with that of Natalya Rapoport, a professor of bioengineering at the University of Utah, who has been studying the physics and chemistry of drug delivery using water-soluble plastics called micelles. Made of polyethylene oxide and polypropylene oxide, micelles are a self-assembled collection of molecules that spontaneously form tiny plastic spheres when introduced into water.

In previous work, Pitt and Rapoport found that an anti-cancer drug called doxorubicin is averse to water and seeks "protection" inside the micelles when both are mixed in water. They hypothesized that the drug, safely encapsulated in microscopic micelle "vehicles," could be injected into a cancer patient and travel through the bloodstream without any side effects. At an appointed time, a physician could apply ultrasound to a tumor and release the drug to that tumor site only.

After successful trials in test tubes, Pitt had a graduate student, Jared Nelson, inject doxorubicin contained within the plastic micelle carrier and apply various levels of ultrasound to cancer tumors placed in rats' legs. The size of the tumor was measured and observed over the four-week treatment period. At the experiment's conclusion, Pitt and Nelson found that the application of the drug in combination with ultrasound significantly reduced the tumor size when compared to tumors that were not exposed to ultrasound.

"We believe that ultrasound releases the DOX from the micelles and that it could also be assisting the drug to enter the tumor cells," said Nelson, who became an associate scientist for pharmaceutical company Pfizer after completing the study and graduating in April.

"This research shows that ultrasound can be used to selectively release one kind of anti-cancer drug at a tumor site and reduce the size of that tumor in a rat model," said Pitt. "We are excited about the findings, but still need to optimize the process before we take it to the next step."

If further experiments prove successful, the method would be tested on other animals using different kinds of drugs and ultrasound frequencies before trials on humans could begin, a prospect that is still several years away.

Beverly Roeder, a veterinarian and BYU professor of integrative biology, helped develop the procedure to do this study on tumors in rats. John Carmen, a master's student in microbiology and Friederike Roloff, an undergraduate in microbiology at the time of the study, helped with the study and co-authored the "Cancer Research" article that appears in the Dec.15 issue. Their study was funded by the BYU Cancer Research Center. Further funding from the National Institutes of Health via a grant to Rapoport at the University of Utah will enable Pitt's laboratory to continue research in this area.

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