title: Development of oral self nano-emulsifying delivery system(s) of lanreotide with improved stability against presystemic thiol-disulfide exchange reactions.
abstract: To develop a self nano-emulsifying delivery system (SNEDS) for model peptide lanreotide providing a protective effect towards thiol-disulfide exchange reactions.
  
  
  
  Ion-paired complexes of lanreotide with surfactants were prepared. In the following, Log P (octanol/water) of these complexes was determined. Lanreotide-loaded SNEDS (Lan/Deo-SN2 and Lan/Deo-SN3) were characterized for payload, droplet size and zeta potential. Lan/Deo-SN2 and Lan/Deo-SN3 were incubated with reduced glutathione (GSH) and thiol-enriched casein peptones for the assessment of thiol-disulfide exchange reactions. Ultra-centrifugation was used for separation of lanreotide released from SNEDS.
  
  
  
  A maximum payload of 6.4% was achieved for Lan/Deo-SN2. Mean droplet size of Lan/Deo-SN2 and Lan/Deo-SN3 was 45 ± 0.20 nm and 37 ± 0.02 nm, respectively. Both formulations showed significant protection towards thiol-disulfide exchange reactions. After 3 h of incubation with GSH, 48% and 80% of lanreotide remained intact when incorporated in Lan/Deo-SN2 and Lan/Deo-SN3, respectively. Furthermore, Lan/Deo-SN2 and Lan/Deo-SN3 showed 47% and 51% protection against thiol enriched casein peptones, respectively. Both formulations showed sustained lanreotide release over a period of 3 h.
  
  
  
  Owing to the results, the above-mentioned approach might be a useful tool to overcome the sulfhydryl barrier of the GI-tract.
authors.affiliation: a Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy , University of Innsbruck , Innsbruck , Austria.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ijaz
authors.affiliation: a Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy , University of Innsbruck , Innsbruck , Austria.
authors.forename: Sonja
authors.initials: S
authors.lastname: Bonengel
authors.affiliation: a Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy , University of Innsbruck , Innsbruck , Austria.
authors.forename: Ožbej
authors.initials: O
authors.lastname: Zupančič
authors.affiliation: a Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy , University of Innsbruck , Innsbruck , Austria.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Yaqoob
authors.affiliation: b Center for Chemistry and Biomedicine, Institute of Biochemistry , University of Innsbruck , Innsbruck , Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Hartl
authors.affiliation: c Center for Chemistry and Biomedicine, Institute of Analytical Chemistry and Radiochemistry , Leopold-Franzens University , Innsbruck , Austria.
authors.forename: Shah
authors.initials: S
authors.lastname: Hussain
authors.affiliation: c Center for Chemistry and Biomedicine, Institute of Analytical Chemistry and Radiochemistry , Leopold-Franzens University , Innsbruck , Austria.
authors.forename: Christian W
authors.initials: CW
authors.lastname: Huck
authors.affiliation: a Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy , University of Innsbruck , Innsbruck , Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bernkop-Schnürch
mesh_terms: D004220:Disulfides / Q000737:chemistry; D004655:Emulsions; D005978:Glutathione / Q000737:chemistry; D006801:Humans; D010084:Oxidation-Reduction; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry; D010456:Peptides, Cyclic / Q000008:administration & dosage* / Q000737:chemistry; D013004:Somatostatin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry*
chemical_list: D004220:Disulfides; D004655:Emulsions; D010455:Peptides; D010456:Peptides, Cyclic; D013438:Sulfhydryl Compounds; D013501:Surface-Active Agents; C060347:lanreotide; D013004:Somatostatin; D005978:Glutathione
keywords: Lanreotide acetate; glutathione; ion pairing; self nano-emulsifying delivery system; thiol-disulfide exchange reactions