Inclusive Dates: 10/01/99 - 09/30/01
Background - The oral delivery of new protein or peptide drugs is highly desirable in providing a convenient dosing method. Currently, these drugs are limited in oral applications because they are degraded in the gastrointestinal tract by gastric acidity and enzymatic attack.
Approach - This project was conducted in conjunction with the Centers for Disease Control (CDC) in Atlanta, Georgia. A good model for oral protein drug delivery is a rabies antigen, which is degraded in the gastrointestinal tract by gastric acidity and enzymatic attack. The CDC agreed to supply the antigen and to conduct animal tests on the formulated dosage form. The approach was to encapsulate the antigen in small (less than ten micrometers) particle size for delivery to the intestinal tract. The intestinal tract contains groups of cells called Peyer's patches, which can absorb solid particles less than ten micrometers in size. The theory was for the Peyer's patches to absorb the small capsules and then release the antigen into the blood stream. Using a delivery system patented (U.S. patents 5,382,435 and 5,505,967) and owned by the Institute, the research team encapsulated the small capsules in a larger particle designed to provide additional protection in the stomach. At the CDC, these particles were fed to mice, and the mice were then tested for rabies resistance.
Accomplishments - Small capsules containing the rabies antigen were prepared using a biodegradable polymer. The capsules, less than ten micrometers in size, were contained in an enteric coating for protection in the stomach. The antigen capsules, along with a placebo, were sent to the CDC for testing. Initial tests indicate that no antigen was present in mice for four weeks after oral administration of the capsules. One possible explanation is that, due to the rapid metabolism rate of the mice, the larger particles did not have time to disintegrate and release the small antigen capsules for absorption. To resolve this problem, the CDC is conducting additional testing on a modified formulation.