Development of Drug Delivery Systems for the Peroral Administration of Peptide and Protein Drugs

The oral bioavailability of peptide and protein drugs is normally very low. Therefore such drugs often have to be administered via the parenteral route. However, parenteral administration often causes discomfort and is even very painful for the patient. Hence, the development of efficient oral delivery systems for peptide and protein drugs represents a great challenge in pharmaceutical technology. The basic idea of the strategy followed within this project was to incorporate peptide and protein drugs in an appropriate carrier matrix which should then be channeled through the digestive tract to the small intestine. There the carrier matrix should adhere on the mucosa and the incorporated drug should be released. After paracellular permeation (i.e. through the space between the enterocytes) to the underlying blood vessels the drug will be channeled directly to the liver via the portal vein. However, on its way the peptide/protein drug has to be protected from the attack of digestive enzymes. Otherwise the drug would be digested like nutritive proteins and consequently inactivated. Within the project it could be shown that the paracellular permeation of peptide/protein drugs could be significantly improved by the use of certain unabsorbable polymers-so-called "thiolated polymers"-which stick to the intestinal wall very strongly. In further studies regarding the permeation enhancing effect of "thiolated polymers" also the underlying mechanism could be enlightened. Further, polymers with strongly improved enzyme inhibitory properties have been developed. Based on the permeation enhancing and enzyme inhibiting polymers an oral delivery system for insulin has been developed. The efficacy of such test-tablets could be shown in vivo in diabetic mice impressively. Within 80 hours the blood glucose level of the mice could be decreased 20 to 40 percent after the administration of just one insulin- tablet. Due to the findings derived from the project, an efficient oral delivery of peptide and protein drugs seems to be feasible. A company has to be raised in the very near future, which will start the manufacturing of oral insulin, after further experiments, prescribed drug-examinations as well as official registration procedures have been performed.