Experts told UPI's Nano World the reactors - consisting of capsules only nanometers or billionths of a meter in size - could boost the efficiency of medicine synthesis by five-fold or more.

"If making drugs becomes more efficient, hopefully that will be converted to cheaper prices for consumers," said chemist Tyler McQuade of Cornell University in Ithaca, N.Y., who is developing a nanotech reactor for pharmaceutical manufacturing.

The pharma industry typically generates more than 25 pounds of waste for every pound of medicine produced - proportionally more than any other industry, according to the pharmaceutical giant Pfizer in New York, McQuade said.

"A pharmaceutical company produces only a small fraction of waste that, say, a refinery produces, but from a refinery, only a tenth of a kilogram of waste is generated for every kilogram of product," he explained.

Left untackled, the pharmaceutical-waste problem will continue to grow, because nearly all drugs not produced naturally are made from petroleum.

"Of the top 200 drugs, greater than 90 percent are produced from oil," McQuade said. "They're refined oil, essentially, and if oil prices continue to go the way they're going, pharmaceutical agents are going to become more expensive over the next 10 to 50 years, and the need to make pharmaceutical agents more efficiently will become important."

To increase drug-synthesis efficiency, McQuade and his lab are developing microscopic nylon-like capsules, each of which contains a different catalyst, such as an enzyme or the elements palladium or cobalt. The capsules are porous, so reactants and end-products can flow in and out.

Varying a capsule's traits such as pore size can keep the wrong chemicals from entering and fouling the reaction. To make sure the catalyst stays inside the capsule, it is attached to a polymer string.

"Think of a basketball full of spaghetti," McQuade said. "The spaghetti can't get out, but small molecules can still get in."

The idea is to make a series of capsules, each of which performs one of the many steps used to create a specific drug, then combining the right capsules together in a single pot, so drugs can be synthesized in one step rather than, say, five.

McQuade hopes to patent the single-step capsule-synthesis process by the end of February.

"So why does having a series in one reactor vs. many save waste?" McQuade asked. "It turns out the largest instance of waste in pharmaceutical production is the solvent - the liquid you run the reactions in. What you would like to do is to run all the reactions in the same solvent, and all at once."

McQuade said he expects the drug-production efficiency to scale up according to how many steps the capsules help cut.

"For instance," he explained, "if you have a five-step synthesis, and each step requires five different solvents, then at minimum you can reduce waste by a factor of five. The numbers of vessels you have to maintain also go down, along with the plumbing parts, and you also reduce the volatile organic compounds you generate as you move reactors around that can end up exposed to workers, the plant and inevitably the environment."

The nanotech process McQuade is developing "is a very important breakthrough technology that should be further elucidated," said Paul Anastas, director of the Green Chemistry Institute in Washington, D.C.

"It's extremely promising. You have the capacity here to reduce waste and energy use and increase your time and space, which are good environmentally and economically."

Anastas added that McQuade's work "is an excellent example of the fundamental, innovative science that is the hallmark of green chemistry."

The first drug McQuade and colleagues are currently looking to make in one pot is Prozac. By studying the chemistry of the drug, so far they have managed to simplify the current five-step synthesis process to just three - a patentable process in itself.

"We are still working on the conditions to make Prozac in a one-pot process, on a catalyst we haven't perfected yet," McQuade said. "Within six months, we should have a one-pot process. He added his team is also attempting to synthesize the anti-HIV drug ribavirin in just one step.

So far, the Cornell team has developed both micrometer- and nanometer-sized capsules. "In theory, the nanometer-sized capsules have (a larger) surface-area-to-volume (ratio), to generate greater diffusion of chemicals," McQuade said.

McQuade emphasized his work on microscopic reactors is derived from earlier work by Thomas Chang of McGill University in Montreal, who proposed the notion of artificial cells in 1972 that encapsulated enzymes within capsules.

"He's done it," McQuade said. "(He) uses them to make synthetic kidneys. Our work is a perfect way to extend his work with more catalysts and enzymes."

One concern about the process is the capsules slow the in-and-out movement of molecules too much.

"We tried a reaction with an enzyme," McQuade explained. "The reaction without the shell took five hours and with the shell the time was doubled, which is not the end of the world, as the process was not even optimized yet."

Another concern: Catalysts can help enable up to millions of reactions, but even catalysts break down after a while, so capsules with degraded catalysts will have to be regenerated or removed from vats.

"The nice thing about working with these capsules is the potential of making them a range of sizes, and to have the catalysts be of different kinds," McQuade said.

"So if the enzyme catalysts go bad the fastest in a pot, you might be able to sieve them out if they're in the largest capsules, for instance," or by centrifuging them out.

McQuade plans to start his own company, called Sustainable Pharmaceutics, based on his technology. He will discuss the capsules with venture capital firms later this month, and recently talked with a startup company about the possibility of placing reactor capsules in the body that could degrade over time and release drugs.

He cautions, however, that his work remains on the frontier of research.

"It's new and has promise," he said, "but the bottom line is that it has not been peer-reviewed yet, but that should change in the ne xt three months as papers come out."

Nano World is a weekly series by UPI examining the exploding field of nanotechnology, by Charles Choi, who covers research and technology for UPI Science News. E-mail: [email protected]

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