Erodible plastic microspheres could be effective oral drug delivery system

given orally to the rats, the scientists found dicumarol first appeared in the bloodstream within two hours and persisted for three days. For insulin, blood sugar levels were reduced within two hours. The plasmid DNA was incorporated into cells of the liver and small intestine and produced an active protein within five days.

Moreover, use of the microspheres greatly enhanced the drugs' availability in the bloodstream. For example, the increase in activity of dicumarol could be explained by intestinal uptake of up to 47 percent of the microspheres after feeding. Usually, when dicumarol is administered orally, very little of it is absorbed. In the study, the dicumarol also remained in plasma for much longer periods than other forms of the drug orally dispensed to the animals, resulting in improved availability. Insulin and plasmid DNA cannot be administered orally because they are degraded by the harsh conditions of the intestinal tract.

Potential applications of this drug delivery system--to replace therapeutic agents not taken orally today--exist in gene therapy and in the use of vaccines; in treating AIDS, cancer and diabetes; and for delivering medication to inflamed intestines. Proteins, such as insulin, growth hormone, and erythropoetin (used to treat anemia) are examples of drugs that would benefit from this new form of oral delivery. The delivery of corrective gene sequences in the form of plasmid DNA could provide convenient therapy for a number of genetic diseases such as cystic fibrosis and hemophilia.

Edith Mathiowitz, who led the study, thinks the enhanced absorption relates in part to the small size of the spheres and the adhesive nature of the polymers. The spheres were engineered to stick tightly to and even penetrate linings in the gastrointestinal tract before transferring their contents over time into the circulation system.

"The study indicates uptake of entire micro

Contact: Edith Mathiowitz
Brown University

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