Comparison of the protective effect of self-emulsifying peptide drug delivery systems towards intestinal proteases and glutathione

• Published in: International journal of pharmaceutics 2017-05, Vol.523 (1), p.357-365
• Main Authors: Hetényi, Gergely, Griesser, Janine, Moser, Michael, Demarne, Frédéric, Jannin, Vincent, Bernkop-Schnürch, Andreas
• Format: Article
• Language: English
• Subjects: Deamino Arginine Vasopressin - chemistry; Dioctyl Sulfosuccinic Acid - chemistry; Drug Delivery Systems; Drug Liberation; Emulsifying Agents - chemistry; Glutathione - chemistry; Insulin - chemistry; Intestines - enzymology; Leuprolide - chemistry; Peptide Hydrolases - chemistry
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2017.03.027

[Display omitted] •Independent from the type of peptide, all the SEDDS showed a prolonged release.•SEDDS can provide a 100% protective effect towards protease degradation and deactivation by reduced glutathione.•Hydrophilic enzymes and reduced glutathione were not soluble in the oily phase of the SEDDS.•Degradation is only taking place once the drug has left the protective environment of the drug carrier system. 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). 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. 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. 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.