by P. Smaglik
Coating insulin with a layer of plastic the width of a few human hairs could allow diabetics to swallow the medicine that they now must inject several times daily. Such plastic coverings can protect a variety of fragile drugs that would otherwise fall apart on their trip through the stomach, scientists report this week.
In tests involving a range of drugs, researchers found that beads successfully carried molecules of various sizes -- a tiny blood coagulant, medium-sized insulin, and relatively massive DNA molecules -- into rats' bloodstreams, says Edith Mathiowitz. The molecular biologist and her colleagues at Brown University in Providence, R.I., developed and tested beads made of a polyanhydride copolymer of fumaric and sebacic acid that is similar to the casing of ballpoint pens. The results of their work appear in the March 27 Nature.
Scientists have been searching for better ways to deliver protein-based drugs, such as insulin, and other molecules, like DNA, that cannot withstand contact with digestive enzymes. They have manufactured injectable microspheres for delivering proteins (SN: 7/27/96, p. 63), and DNA has been encapsulated in microspheres of an erodable biopolymer called PLG, then successfully fed to mice (SN: 5/11/96, p. 302). Mathiowitz's approach now makes possible oral delivery of medicine in a package that can cling to specific tissues.
The spheres' small size, ranging in diameter from 0.3 to 2 micrometers, allows them to slip between cells and bury themselves in the intestinal walls. Once attached to the tissues, the spheres' shells erode, slowly releasing the contents into the bloodstream.
Mathiowitz and her team of researchers were surprised by the spheres' ability to move through the body. "They can really pass through and penetrate the bloodstream," Mathiowitz says. The scientists wrapped gold in the plastic, then fed the spheres to rats. When the scientists tracked the gold markers with an electron microscope, they found that some spheres reached the spleen and liver -- beyond the expected final stop at the intestinal walls.
Before diabetics can use microspheres instead of syringes, the scientists want to discover a way to make the spheres stick to the intestinal walls. They must also learn how to control the rate of drug release from the beads, Mathiowitz says. "If we can understand the mechanics, I'm sure we can work it out."
Solving those problems could improve the quality of life for the approximately 4 million people in the United States who inject insulin, says Philip E. Cryer, president of the American Diabetes Association in Alexandria, Va.
Robert Langer, a chemical engineer at the Massachusetts Institute of Technology, says the new study gives "real insight" into how bioadhesive microspheres are taken up by tissues. He calls the possibilities of the beads' use in oral gene therapy "potentially very exciting."
Judith H. Greenberg, a geneticist at the National Institutes of Health in Bethesda, Md., says that, although scientists need to answer many questions, the technique holds promise for gene therapy. "It does keep the DNA from being degraded, and it seems to promote getting the DNA into the cell," Greenberg says.
Mathiowitz, E., et al. 1997. Biologically erodable microspheres as potential oral drug delivery systems. Nature 386(March 27):410.
Raloff, J. 1997. New glucose test on the way for diabetes. Science News 152(March 29):190.
1996. A shot in the arm for protein delivery. Science News 150(July 27):63.
Travis, J. 1996. Swallowing shigella: Can bacteria that cause food poisoning deliver oral DNA vaccines? Science News 149(May 11):302.
American Diabetes Association
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Judith H. Greenberg
National Institutes of Health
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Massachusetts Institute of Technology
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Department of Molecular Pharmacology, Physiology and Biotechnology
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