June 30, 1998 WEST LAFAYETTE, Ind. -- The next star in drug delivery and medical technology may be a new material developed by Purdue University researchers. Kelley Keys, a chemical engineering graduate student, has made new gels from a material called a star polymer. The gels' potential applications include removing substances such as cholesterol from the blood and delivering high concentrations of drugs to specific areas in the body, such as tumors.
Keys, a Carmel, Ind. , native, presented her research results Wednesday (6/24) at a meeting of the Controlled Release Society in Las Vegas.
Most polymers are large molecules made up of smaller molecules linked together in a chain, but a star polymer has a central core with many arms radiating out from it. The end of each arm can be very chemically reactive, and it can bind with materials such as cells, drugs, proteins and antibodies.
"The large number of arms in a very small volume would make these star polymers very useful in biological and pharmaceutical applications, such as delivering a high concentration of drugs throughout the body or to a specific target," Keys says.
The star polymer gels Keys developed are made from the polymer polyethylene glycol, or PEG, a nontoxic, noncarcinogenic substance used in many biomedical applications. A few of the up to 70-some arms on each star molecule are used to bind them together to form the gel, leaving the majority of the arms free to react. The average diameter of an individual PEG star molecule is less than 50 nanometers, 100 times smaller than a red blood cell.
An important new property of some of these gels is that they can recognize and remember specific substances through a process called molecular imprinting, a technique developed by other researchers over the past five years.
"During the preparation of the star polymer gels, we add molecules of a particular drug or protein," explains Nicholas Peppas, Keys' faculty adviser and the Showalter Distinguished Professor of Biomedical Engineering at Purdue. "The reactive ends of the star polymer's arms rearrange themselves around the molecule. When we leach out the drug or protein, the polymer remains in that configuration. Later, if we pass the same drug or protein over the gel, the polymer recognizes the molecule and binds to it."
In her experiments, Keys imprinted a gel with the drug proxyphylline, a bronchodilator used to increase the lungs' ability to take in air. Her results showed that the gel "remembers" the proxyphylline and rebinds to the drug at a very high rate. She also passed several other similar drugs through the imprinted gel, but they did not bind to it. The gel can be imprinted with a variety of substances, but once imprinted, it cannot be modified to recognize a substantially different molecule, Peppas says.
Peppas says one future use of the gel would be to imprint it to recognize low-density lipoproteins, or LDLs, which are linked to cholesterol formation in arteries. The gel then could absorb and remove these substances from the blood in a dialysis-type procedure, or perhaps work in the body to move these substances away from danger areas, such as the aorta.
Peppas says another future use for star polymer gels might be to deliver high concentrations of cancer-fighting drugs to a tumor.
"One could imprint a gel so that some of the arms recognize specific cancerous cells, while other arms in the same gel carry an anti-cancer drug," he says. "These gels also could be used as a surface coating, such as on an artificial organ, to provide additional binding sites for cells or antibodies."
Keys used gamma radiation to coax the star polymers into forming a gel, which is a new method of gel preparation. Her methods give the gels superior mechanical stability while maintaining a large number of active groups on the arms, Peppas says.
Keys' research is funded by the Showalter Foundation.
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