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

Aim

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 – 3.9 μm and a zeta potential of -25 mV to -33 mV. All formulations provided a sustained release of the peptides over 6 hours. 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.

Conclusion

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.

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