The use of thiolated polymers as carrier matrix in oral peptide delivery—Proof of concept
| Autor: | Christian W. Huck, Gudrun Schöffmann, Yvonne Pinter, Maria Dorly Del Curto, Mauro D'Antonio, Hermann Kahlbacher, Pierandrea Esposito, Maximilian Schuh, I. Schmerold, Davide Guggi, Andreas Bernkop-Schnürch |
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| Rok vydání: | 2005 |
| Předmět: |
Drug
Polymers Swine Injections Subcutaneous media_common.quotation_subject Administration Oral Biological Availability Pharmaceutical Science Chitin Pharmacology In vivo Oral administration Mucoadhesion Animals Chymotrypsin Trypsin Dissolution testing Sulfhydryl Compounds media_common Drug Carriers Pancreatic Elastase Chemistry Controlled release Pepsin A Bioavailability Injections Intravenous Oligopeptides Conjugate |
| Zdroj: | Journal of Controlled Release. 106:26-33 |
| ISSN: | 0168-3659 |
| Popis: | It was the aim of this study to develop an oral delivery system for the peptide drug antide. The stability of the therapeutic peptide towards gastrointestinal peptidases was evaluated. The therapeutic agent and the permeation mediator glutathione were embedded in the thiolated polymer chitosan-4-thio-butylamidine conjugate (chitosan-TBA conjugate) and compressed to tablets. Drug release studies were performed in the dissolution test apparatus according to the Pharmacopoeia Europea using the paddle method and demineralized water as release medium. In order to avoid mucoadhesion of these delivery systems already in the oral cavity and oesophagus tablets were coated with a triglyceride. These tablets were orally given to pigs (weight: 50+/-2 kg; Edelschwein Pietrain). Moreover, antide was administered intravenously, subcutaneously and orally in solution. Results showed stability of antide towards pepsin, trypsin and chymotrypsin. In contrast, antide was rapidly degraded by elastase. Consequently a stomach-targeted delivery system was designed. Drug release studies demonstrated an almost zero-order controlled release of antide over 8 h. In vivo studies demonstrated a relative bioavailability of 34.4% for the subcutaneous administration. Oral administration of antide in solution led to no detectable concentrations of the drug in plasma at all. In contrast, administering antide being incorporated in the thiolated polymer resulted in a significant uptake of the peptide. The absolute and relative bioavailability was determined to be 1.1% and 3.2%, respectively. |
| Databáze: | OpenAIRE |
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