title: Comparison of the protective effect of self-emulsifying peptide drug delivery systems towards intestinal proteases and glutathione.
abstract: OBJECTIVE
  The aim of this study was to evaluate the protective effect of self-emulsifying drug delivery systems (SEDDS) for therapeutic peptides towards intestinal proteases and reduced glutathione (GSH).
  
  
  METHODS
  Sodium docusate was applied as anionic surfactant for hydrophobic ion pairing with leuprorelin (LEU), insulin (INS) and desmopressin (DES). The complexes were loaded into SEDDS that were characterized regarding droplet size distribution and zeta potential. The release profile of the peptides was examined by dialysis membrane method. Enzymatic digestion studies were performed by applying α-chymotrypsin, trypsin and elastase. Furthermore, the protective effect of SEDDS towards degradation through thiol-disulfide exchange reactions was examined by addition of GSH.
  
  
  RESULTS
  SEDDS showed a mean droplet size of 0.27-3.9μm and a zeta potential of -25 to -33mV. All formulations provided a sustained release of the peptides over 6h. Degradation of the model peptides by intestinal proteases and GSH could only be observed in the release medium. In the oily phase of SEDDS neither any of the proteases nor GSH was soluble (≤0.1%). Furthermore, no degradation of the model peptides by proteases and GSH took place in the oily phase of SEDDS.
  
  
  CONCLUSIONS
  SEDDS can provide a 100% protective effect towards protease degradation and deactivation by GSH. According to this, SEDDS might be promising tools for oral delivery of peptide drugs.
authors.affiliation: Thiomatrix Forschungs-und Beratungs GmbH, Trientlgasse 65, Innsbruck, Austria.
authors.forename: Gergely
authors.initials: G
authors.lastname: Hetényi
authors.affiliation: Thiomatrix Forschungs-und Beratungs GmbH, Trientlgasse 65, Innsbruck, Austria.
authors.forename: Janine
authors.initials: J
authors.lastname: Griesser
authors.affiliation: Thiomatrix Forschungs-und Beratungs GmbH, Trientlgasse 65, Innsbruck, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Moser
authors.affiliation: Gattefossé SAS, 36 chemin de Genas 69804 Saint-Priest Cedex, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Demarne
authors.affiliation: Gattefossé SAS, 36 chemin de Genas 69804 Saint-Priest Cedex, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Jannin
authors.affiliation: Thiomatrix Forschungs-und Beratungs GmbH, Trientlgasse 65, Innsbruck, Austria; Center for Chemistry and Biomedicine Department of Pharmaceutical Technology Institute of Pharmacy University of Innsbruck, Innrain 80/82 6020 Innsbruck, Austria. Electronic address: andreas.bernkop@uibk.ac.at.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bernkop-Schnürch
mesh_terms: D003894:Deamino Arginine Vasopressin / Q000737:chemistry*; D004143:Dioctyl Sulfosuccinic Acid / Q000737:chemistry; D016503:Drug Delivery Systems; D065546:Drug Liberation; D045703:Emulsifying Agents / Q000737:chemistry; D005978:Glutathione / Q000737:chemistry*; D007328:Insulin / Q000737:chemistry*; D007422:Intestines / Q000201:enzymology; D016729:Leuprolide / Q000737:chemistry*; D010447:Peptide Hydrolases / Q000737:chemistry*
chemical_list: D045703:Emulsifying Agents; D007328:Insulin; D004143:Dioctyl Sulfosuccinic Acid; D010447:Peptide Hydrolases; D016729:Leuprolide; D003894:Deamino Arginine Vasopressin; D005978:Glutathione