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Tying up proteins for drug delivery.

Tying up proteins for drug delivery

A group of Ohio researchers has devised a way to wrap protein drugs in a protective coating so that the proteins can be taken orally rather than by injection. The wrap has potential as a way to free diabetics from daily insulin shots, and may also prove useful for other proteins, including painkillers, certain vaccines and new contraceptives, the researchers say.

What the digestive system does to proteins is good for digestion, but not good for protein drugs. Enzymes and high acid levels in the stomach followed by alkalinity in the small intestine break proteins down into their constituent amino acids, which are absorbed into the blood for use in the body. Protein drugs will be broken down by the same process, losing their activity before they get into the blood. As a result, therapeutic proteins such as insulin must be injected in order to sidestep the protein-destroying gut.

Researchers from the Medical College of Ohio in Toledo and Bowling Green State University noticed that nonprotein drugs used to treat diseases of the large intestine contain chemical bonds called azoaromatic bonds, which enable them to reach their target organ intact. The bond is a double link between nitrogen atoms, each of which is hooked to ring-containing hydrocarbon chains. Azoaromatic bonds are also found in many yellow, orange and red food colorings.

The researchers selected an azoaromatic polymer to coat insulin pellets and capsules containing another protein hormone involved in urine production. The coated compounds carried the drugs safely through the stomach and small intestine and into the large intestine of rats, where the coating was broken down by bacteria normally present in the gut. Insulin is known to be able to cross the wall of the large intestine into the blood in both non-diabetic and diabetic people.

The drugs caused the intended physiological responses--lowered blood sugar and decreased urine production --but not in a highly uniform fashion, the researchers report in the Sept. 5 SCIENCE. The responses began from one to nine hours following ingestion, an irregularity that will have to be ironed out if the process is to be useful.

"I think we can control this by engineering the polymer,' says Douglas C. Neckers, a Bowling Green chemist who is working on the project. While some researchers have suggested that the body could develop antibodies to the insulin, other studies indicate that it won't be a problem, Neckers says.

Before azoaromatic coatings can be used in the treatment of diabetes or any other protein-requiring condition in humans, animal trials will have to be done. "In two or three years,' says Neckers, "we'll know a little more about its potential.'
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Author:Silberner, Joanne
Publication:Science News
Date:Sep 6, 1986
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