Because chemotherapy takes such a heavy toll on the body, scientists have been working on ways to deliver drugs directly to tumor sites, bypassing healthy organs. But they'd also like a way to control the release of drugs from delivery devices. Better dosing control could decrease the side effects of toxic drugs and make treatment more effective.

SIUC materials scientist Lori Vermeulen thinks a well-known and safe material, clay, and a well-known and safe technology, ultrasound, might be used to externally control the delivery of drugs from implants or carrier medications.

An expert on designing and synthesizing layered materials and polymers, Vermeulen was familiar with studies showing that ultrasound could activate drug release from polymer implants. To exploit ultrasound as a tool for controlling drug release, she knew scientists would need to develop a broader materials base for drug delivery. She thought that natural or synthetic clays might fit the bill.

Clays, which are layered inorganic materials, can be induced to host certain organic chemical compounds ("guests") in the tiny gaps between the layers. Ultrasound, she thought, might be used to activate and control the release of guest drug compounds from clay materials.

"Things stick to clay. The idea is to stick the drug to it and release the drug the way you want to," she explains. "From a chemist's point of view, it's easy to modify the structure of the host to suit the drug."

To test her hypothesis, Vermeulen's lab team introduced several different guest compounds, including two containing biologically active molecules, into samples of a clay called montmorillonite. They suspended the clay samples in water and then applied ultrasound. They found that they could affect how rapidly and completely a guest compound was released from a sample by varying the ultrasound frequency.

The team also got promising results with some synthetic clay-like materials that Vermeulen designed. These materials, called metal phosphonates, are layered like clay. But because they can be designed to carry a wider range of guest compounds, including proteins, they might prove to be a more versatile class of materials for drug delivery.

The specific chemical and physical features of each clay compound determine how these hybrid materials respond to ultrasound, Vermeulen says. For example, ultrasound breaks down the particle size of the guest compound in some of the samples, but not others.

Such factors, along with environmental factors in the body, will determine the rate and degree of drug release. But Vermeulen's research suggests that it can be regulated. And clays are biologically inert, making them a benign substance for use in the body.

Vermeulen's proof-of-concept studies were funded by a grant from the American Cancer Society. Master's student Patricia Calloway, now a chemist with Eli Lilly Co., did much of the lab work and is writing her thesis on it.

Vermeulen plans to continue designing, synthesizing, and analyzing various combinations of hosts and guests and testing them with a range of ultrasound frequencies. Ben Baptist, a chemistry major, has an undergraduate assistantship to help with the research. Although their investigations are still at a very early stage, Vermeulen hopes it will be possible to design materials that can work in practice to deliver specific anticancer drugs.

--Marilyn Davis

> Spring 2004 cover story on cancer research