ENGINEERS CREATE PROMISING NANOTECHNOLOGY FOR ORAL DELIVERY OF CANCER DRUGS
22 July 2003 - University of Texas at Austin

Jay Blanchette, a biomedical engineering doctoral student working in the laboratory of Dr. Nicholas Peppas, presented the new findings in a paper which earned him the prestigious CRS-Capsugel Graduate/Postdoc Award for innovative aspects of gastrointestinal drug absorption and delivery.

Such nanospheres, known as “carriers” for their ability to transport a drug agent safely through a hostile chemical environment, are suited to formulation into capsules or tablets for oral consumption.

Most chemotherapy treatments are now administered through either multiple daily injections or infusion (injection over a period of several hours) because the drugs quickly break down in the acidic environment of the digestive system.

Blanchette and Peppas, professor of chemical engineering, biomedical engineering and pharmaceutics, have devised a new category of carrier nanospheres designed to overcome that obstacle. They created their spheres from hydrogels: stable organic materials which swell at a rate dependent on the relative acidity of their environment. As a drug-laden hydrogel swells, it releases its drug.

The researchers synthesized co-polymer nanospheres from a dilute solution of two hydrogel monomers, polyethylene glycol and methacrylic acid, in the presence of the chemotherapeutic agent bleomycin. Bleomycin was incorporated into the structures during the process of nanosphere formation under exposure to ultraviolet light.

Next, in vitro experiments were conducted under conditions simulating the passage of the bleomycin-packed nanospheres through the gastrointestinal tract from the stomach (highly acidic) to the upper intestine (barely acidic) over a several-hour period. The results point to the nanospheres as potentially viable elements in an ingestible capsule- or tablet-based controlled-release system. Such a delivery system would take cues from the acidity of its bioenvironment as it moved through the digestive passages, swelling rapidly and releasing most of its beneficial cargo into the upper small intestine to be absorbed into the bloodstream.

While stressing that a great deal more basic research needs to be conducted, Blanchette envisions a day when orally administered chemotherapy drugs will yield comparable efficacy, while reducing side effects and eliminating much of the inconvenience and discomfort of outpatient cancer treatment regimens.

“If you can replace the need to go to the hospital for the injections or infusion on a regular basis, with medication that can be taken in pill or capsule form at home, that’s a vast improvement in quality of life for the patient,” he said.

He added that nanosphere composition can be tailored to deliver specific chemotherapeutic agents.

“When you’re mixing the components used to form the nanospheres, you can change the relative amount of each to accommodate different properties,” he said.

Studies with the widely used agent Alpha Interferon are underway.

Peppas holds the title of Paul D. & Betty Robertson Meek Centennial Professor of Chemical Engineering, Biomedical Engineering and Pharmaceutics. Blanchette is a Ph.D. candidate in biomedical engineering and a Thrust Fellow of the university. The research was funded by the National Institutes of Health.

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