Nanotechnology purifies drugs

In a paper published in Science, Charles Martin, a University of Florida professor of chemistry, two UF graduate students in chemistry and two researchers at VTT Biotechnology in Espoo, Finland have demonstrated how a membrane based on nanotechnology could be used to separate a drug molecule from its enantiomer, or twin pair.

Today, drug makers use several techniques to make antibiotics, chemotherapy drugs and other widely used pharmaceuticals. A common method is to nurture and grow bacteria that produce the desired drug molecule in a mixture. The hitch is this mixture also may contain tens or hundreds of unwanted and potentially harmful molecules or materials, sometimes including the bacteria themselves. As a result, the drug has to be separated from the mixture, or purified - a slow and expensive process.

The workhorse technology now used for purifying drugs, called chromatography, involves letting the mixture flow slowly down a column. Different compounds descend at different speeds, so as a mixture drips down the column, its molecules separate into pure bands. The desired drug can then be captured as a purified band. The process requires considerable use of expensive solvents and also is difficult to use for large-scale production. As a result, researchers have for some time discussed replacing chromatography with a membrane that would automatically capture the desired drug.

Complicating the picture is that most drug molecules are produced in what is known as chiral pairs, with one molecule the mirror image of the other. Typically, only one of the two molecules is beneficial, while the other is benign or even harmful. Before a drug can go on the market, drug makers must either prove the mirror image or 'enantiomer' molecule is harmless or find a way to remove it.

Martin said the Finnish researchers recognised that antibodies, which identify and attack pathogens in the body, are good at identifying and attaching to highly specific molecules. So they engineered an antibody that would attach to the drug in question, an experimental anti-tumour designed for the treatment of breast cancer and currently in clinical trials.

The scientists next needed a way to deploy the antibody so that it could be used to separate the drug molecule from its enantiomeric twin. For that, they turned to Martin, who is known for his research in the science of nanotubes. Martin and the Finnish researchers found a way to attach the antibodies, which measure approximately 5 nanometers, to the inside of the tubes. In tests, they showed that the antibodies then latched onto the desired drug molecule and passed them along through the tube 'like a bucket brigade,' Martin said. The resulting flow of the sought after drug molecule through the membrane was five times faster than its twin enantiomer molecule, he said. Because the desired drug flows through the membrane faster, it is feasible to separate it from the undesired one.

The experiment proves the concept of 'biologically active membranes,' Martin said. For such membranes to become a useful tool in the drug- making industry, both the rate and volume of flow of the desired molecule through the membrane would have to be far higher, he said. The process could reach the industry within five to 10 years.

Chad Mirkin, a professor of chemistry and director of the Institute for Nanotechnology at Northwestern University, agreed the process shows long-term promise.

'It's a fascinating nanotechnology approach to a very difficult separation problem,' Mirkin said. 'If it could be scaled up, it could have enormous potential. It is too early to talk about potential commercial impact.'