In Vitro Cellular Uptake and Insulin Secretion Studies on INS-1E Cells of Exendin-4 Loaded Self Nanoemulsifying Drug Delivery Systems

Exendin-4 (ex-4) is a peptide molecule that regulates blood glucose levels without causing hypoglycemia by providing insulin secretion from beta cells in the pancreas. Self nanoemulsifying drug delivery systems (SNEDDS) attrack attention for oral administration of therapeutic peptide/proteins because they protect therapeutic peptide/proteins from the gastric environment, reduce changes due to food effects, are easy to prepare and scale-up. Ex-4 has no commercial form that can be administered orally. In this study the cytotoxicity, cellular uptake and insulin secretion of ex-4 and ex-4/chymostatin (chym) SNEDDS were investigated on INS-1E rat pancreatic beta cells. The effect of ex-4 and ex-4/chym SNEDDS on cell viability in INS-1E cells increased when the dilution ratio higher. Ex-4 and ex-4/chym SNEDDS increased insulin levels in 2.8 mM (low-dose) glucose-induced INS-1E cells 2.21 and 2.17-folds compared to control, respectively. Ex-4 and ex-4/chym SNEDDS increased insulin levels in 16.7 mM (high-dose) glucose-induced INS-1E cells compared to control, respectively. In cellular uptake studies, coumarin-6 solution penetrated the apical membrane of INS-1E cells and remained in the cytoplasm, while coumarin-6 loaded SNEDDS were visualized in the nuclei of the cell. These findings will likely be useful in the development of new formulations for the oral administration of peptides/proteins.