Development and characterization of exendin-4 loaded self-nanoemulsifying system and in vitro evaluation on Caco-2 cell line

Aim: Aim of this study was to develop exendin-4 and exendin-4/chymostatin loaded self-nanoemulsifying drug delivery system (SNEDDS). Methods: Surfactants and co-surfactants were mixed, oil phase containing exendin-4 or exendin-4/chymostatin was added dropwise for SNEDDS. Short term physical stability test was performed prior to the release, lipolysis and permeability studies. Results: SNEDDS containing ethyl oleate: Cremophor EL(R): Labrasol(R): propylene glycole (15:42.5:21.25: 21.25) were selected for in vitro release and intestinal permeability studies for suitable parameters and physical stability test results. SNEDDS were obtained which yielded Grade B nanoemulsions having droplet size below 25 nm. In vitro release studies showed that 73.79% of the peptide was released for 2 h at pH 6.8. Both exendin-4 and exendin-4/chymostatin loaded SNEDDS were non-toxic to Caco-2 cells. Permeability coefficients of both exendin-4 loaded SNEDDS and exendin-4/chymostatin loaded SNEDDS were higher than exendin-4 solution. Conclusions: Intestinal permeability of exendin-4 has been improved by SNEDDS formulations.