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Gewählte Publikation:

Publikationstyp: Zeitschriftenaufsatz
Dokumenttyp: Originalarbeit

Jahr: 2005

AutorInnen: Bernkop-Schnürch, A; Pinter, Y; Guggi, D; Kahlbacher, H; Schöffmann, G; Schuh, M; Schmerold, I; Del Curto, MD; D"Antonio, M; Esposito, P; Huck, C

Titel: The use of thiolated polymers as carrier matrix in oral peptide delivery--proof of concept.

Quelle: J Control Release. 2005; 106(1-2):26-33



Autor/innen der Vetmeduni Vienna:

Schmerold Ivo
Schöffmann Gudrun
Schuh Maximilian

Beteiligte Vetmed-Organisationseinheiten
Institut für Pharmakologie und Toxikologie
Universitätsklinik für Kleintiere, Klinische Abteilung für Anästhesiologie und perioperative Intensivmedizin
Universitätsklinik für Schweine


Abstract:
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.

Keywords Pubmed: Administration, Oral
Animals
Biological Availability
Chitin/analogs & derivatives*
Chitin/chemistry
Chymotrypsin/metabolism
Drug Carriers/pharmacokinetics*
Injections, Intravenous
Injections, Subcutaneous
Oligopeptides/blood
Oligopeptides/pharmacokinetics*
Pancreatic Elastase/metabolism
Pepsin A/metabolism
Polymers/pharmacokinetics
Sulfhydryl Compounds/chemistry*
Swine
Trypsin/metabolism


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