Gel swells during high-sugar spells.

A soft gel that shrinks and swells in response to changing sugar concentrations could provide a new way to deliver insulin to people with diabetes.

Developed by a team of researchers in Japan, the gel absorbs water when it encounters a high concentration of glucose, a sugar found in the blood. As the gel expands, its pores open and allow insulin inside the gel to escape. Insulin is the hormone, normally secreted by the pancreas, that regulates blood sugar.

Unable to produce insulin, people with type I diabetes suffer from too much blood glucose. They must regularly take insulin by injection or from mechanical pumps that deliver a dose of the hormone at the press of a button.

An ideal device would control itself, administering insulin automatically according to prevailing conditions in the blood, says Sung Wan Kim of the University of Utah in Salt Lake City, who designs polymers for drug delivery. A gel such as the one made by the Japanese group could do just that, he says, if animal tests support the laboratory findings.

The Japanese team's gel consists of a liquid polymer that includes phenylboronic acid, a compound that binds to glucose. As glucose attaches to the acid, the resulting molecule acquires a negative charge, increasing the polymer's attraction to water. The gel "undergoes a remarkable change in the swelling," says Kazunori Kataoka of the University of Tokyo.

He and his colleagues load the gel with insulin by immersing it in a solution of the hormone for 24 hours. They can make the gel release insulin on demand in laboratory tests by raising and lowering the glucose concentration around the gel. Kataoka and his coworkers at the Science University of Tokyo and the Tokyo Women's Medical University reported their findings on Nov. 19 in the online version of the Journal of the American Chemical Society.

A few polymers that release insulin automatically have been developed using natural proteins as the glucose-sensing agent, says Kataoka. Because of concerns about the stability of such proteins and the possibility of stimulating an immune attack, these gels have not been tested in humans, he says. "The most important feature of our system is that it consists of [a] totally synthetic polymer gel," which may present fewer problems with patient incompatibility.

The gel could be part of an implant placed in a diabetic person's abdominal cavity, Kataoka explains. The insulin loaded gel would fill a pouch made from a thin membrane that would keep out unwanted proteins and cells but allow glucose and insulin to flow through. When glucose concentrations get too high, the gel would swell and release insulin through the membrane and into the blood.

The current version of the gel only works in alkaline solutions, Kataoka notes, while blood has a pH closer to neutral. He and his colleagues are now testing gels with a derivative of phenylboronic acid that should respond to actual physiological conditions.