Bad bacteria key to drug delivery

Daily Times Monitor

Say “E. coli” in a restaurant and diners scramble for the nearest exit. So why are researchers using the deadly bacteria as an essential ingredient in tiny, implantable drug dispensers?

The reason, say scientists at the University of Arkansas who are developing the alternate method of drug delivery, is that the bacterium is easily mutable. And, they maintain, once genetically altered, it’s completely harmless, reports a web portal.

Implantable drug dispensers reduce the need for repeated insulin or chemotherapy injections and can also provide blood samples for analysis without using needles.

There are a handful of methods in the works to meet the increasing demand for smaller implants.

One uses microelectromechanical systems, or MEMS. With gears no bigger than a grain of pollen, MEMS range in size from mere micrometers to a millimetre. The problem with these devices, however, is that their internal pressure is so high that leaks can occur.

Nonmechanical designs, on the other hand, use electrical voltage to move the fluid around. The problem with these is that they rely on the electrical properties of the fluid and so are limited in the types of drug they can dispense.

The Arkansas team modified E. coli bacterium so that one of its flagella — or tentacles — is tethered to the platform of the nanodispenser. In this way, the bacteria are “planted” in a line within the microscopic channels of the dispenser.

“These bacteria are the world’s smallest living motors — they are only 30 nanometers in diameter,” said Ajay Malshe, an associate professor of mechanical engineering with the University of Arkansas.

The world’s smallest living motor: The bacteria are also genetically modified so they all rotate in the same direction. The spin of the bacteria works to push the drug around and out of the dispenser.

“Natural-occurring E. coli will turn either clockwise or counterclockwise,” said Steve Tung, an assistant professor of mechanical engineering on the development team. “We want to control their rotation so they only turn counterclockwise. We alter their DNA so they all turn in this direction only.”

Still, some reacted sceptically to the idea of using E. coli in this manner.

“If they are going to use E. coli for drug delivery in the body, even if it’s been genetically changed so it’s not harmful, they will have problems getting it approved by the regulatory bodies,” said Carl Grove, president of iMedd, an Ohio company that develops drug-delivery systems.

Ken Chiu, of the department of medicine division of endocrinology at the University of California at Los Angeles, emphasized the importance of making it clear that the strain of bacteria is benign.

“People will be scared to use it, so we would need to be able to convince them that it is completely harmless. This depends on how they have designed the bacteria,” Chiu said.

Tung acknowledged that using E. coli — made notorious in 1993 when Jack in the Box restaurants undercooked hamburgers that killed three people and made dozens of others sick, and in the 1996 Odwalla juice contamination, in which one child died and 60 others became ill — may make people nervous.

But, Tung maintains, the genetically modified strain of the bacteria has been rendered completely harmless. “We specifically point out that these are non-pathogenic. People have bacteria in their bellies that help you digest food — it exists naturally in the body all the time,” he said.

Building a prototype of the implant, however, is not without its challenges, the first of which is sealing the device.

“If the device is open, then the cells live happily. But when we close the device, the cells start to die,” Tung said. He believes it’s a simple matter of designing a better device. Tung said the team would have a working prototype ready within two years. “Commercially, I think it will be ready in five to 10 years,” he said.

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