title: Impact of lipases on the protective effect of SEDDS for incorporated peptide drugs towards intestinal peptidases.
abstract: OBJECTIVE
  The aim of this study is the development of self-emulsifying drug delivery systems (SEDDS) differing in amounts of ester substructures and to evaluate their stability in presence of pancreatic lipase and protective effect against luminal enzymatic metabolism using leuprorelin as model peptide drug.
  
  
  METHODS
  Hydrophobic leuprolide oleate was incorporated into three different SEDDS formulations and their stability towards pancreatic lipases was investigated utilizing a dynamic in vitro digestion model. Protective effect of SEDDS in respect to peptide drug stability against proteolytic enzymes, trypsin and α-chymotrypsin, was determined via HPLC.
  
  
  RESULTS
  Results of in vitro digestion demonstrated that 80% of SEDDS containing the highest amount of ester linkages was degraded within 60min. In comparison to that, SEDDS without ester bonds showed no degradation. With increasing oil droplets hydrolysis the remaining amount of peptide encapsulated into formulation decreased. Furthermore, after 180min incubation with trypsin up to 33.5% and with α-chymotrypsin up to 60.5% of leuprolide oleate was intact while leuprorelin acetate aqueous solution was completely metabolized by trypsin within 120min and by α-chymotrypsin within 5min. Protective effect in environment containing lipases was lower due to oil phase degradation, however, the amount of peptide in ester-free SEDDS was remarkably higher compared to SEDDS susceptible to lipases.
  
  
  CONCLUSIONS
  The present study revealed that SEDDS stable towards hydrolysis is able to exhibit a protective effect for oral peptide delivery.
authors.affiliation: Department of Pharmaceutical Technology, Institut of Pharmacy, Center for Chemistry and Biomedicine, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
authors.forename: Gintare
authors.initials: G
authors.lastname: Leonaviciute
authors.affiliation: Department of Pharmaceutical Technology, Institut of Pharmacy, Center for Chemistry and Biomedicine, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
authors.forename: Ožbej
authors.initials: O
authors.lastname: Zupančič
authors.affiliation: Department of Pharmaceutical Technology, Institut of Pharmacy, Center for Chemistry and Biomedicine, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
authors.forename: Felix
authors.initials: F
authors.lastname: Prüfert
authors.affiliation: Department of Pharmaceutical Technology, Institut of Pharmacy, Center for Chemistry and Biomedicine, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
authors.forename: Julia
authors.initials: J
authors.lastname: Rohrer
authors.affiliation: Department of Pharmaceutical Technology, Institut of Pharmacy, Center for Chemistry and Biomedicine, 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: D000818:Animals; D002918:Chymotrypsin / Q000378:metabolism*; D004339:Drug Compounding / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods*; D065546:Drug Liberation; D004355:Drug Stability; D004655:Emulsions / Q000737:chemistry*; D004952:Esters / Q000378:metabolism; D007422:Intestines / Q000201:enzymology*; D016729:Leuprolide / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D008049:Lipase / Q000378:metabolism*; D013552:Swine; D014357:Trypsin / Q000378:metabolism*
chemical_list: D004655:Emulsions; D004952:Esters; D008049:Lipase; D002918:Chymotrypsin; C117608:alpha-chymotrypsin; D014357:Trypsin; D016729:Leuprolide
keywords: Digestion; Pancreatic lipase; Peptide; Self-nanoemulsifying system; Trypsin; α-Chymotrypsin