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

Abstract

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^®: Labrasol^®: 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.

Keywords:

• Exendin-4
• self-nanoemulsifying drug delivery system
• oral delivery
• lipolysis
• intestinal permeability

Disclosure statement

The authors report no conflicts of interest.

Additional information

Funding

This research was supported by Research Fund of the Erciyes University. Project Number: TCD-2017–7087 and Scientific and Technological Research Council of Turkey (TUBİTAK) Project Number: 217S416.