Glyceryl ester surfactants: Promising excipients to enhance the cell permeating properties of SEDDS.

AIM

The aim of the study is the evaluation of the impact of glyceryl ester surfactants on cell permeating properties of SEDDS (self-emulsifying drug delivery systems).

METHODS

SEDDS containing the glyceryl ester surfactants polyglyceryl-3-stearate (TGlysurf9), polyglyceryl-5-oleate (TGlysurf11.5) and glyceryl stearate citrate (TGlysurf12) were prepared and characterized regarding droplet size and zeta potential. Toxicity studies were performed on Caco-2 cells using resazuring assay. The formulations were loaded with fluorescein diacetate (FDA) and curcumin, and cell uptake studies on Caco-2 cells were performed. Cell uptake was visualized via real time live confocal microscopy. Cell permeability of the SEDDS was tested and trans-epithelial electrical resistance (TEER) measurements were performed. Furthermore, the anti-proliferative and anti-migration activity of curcumin loaded in the SEEDS was investigated.

RESULTS

The developed SEDDS (0.05% m/v) showed no cytotoxicity on Caco-2 cells after 3 h of incubation. Glyceryl esters-SEDDS showed a significant higher FDA and curcumin cell uptake than SEDDS without glyceryl ester surfactants (p < 0.05). TGlysurf9-SEDDS showed thereby the most pronounced permeation enhancing properties. TEER remained constant during the permeation study. Curcumin loaded in TGlysurf9-SEDDS exhibited 1.9-fold higher anti-proliferative effect than curcumin loaded in SEDDS without glyceryl ester surfactants. Furthermore, curcumin loaded in glyceryl ester-SEDDS inhibited Caco-2 cells migration to a higher extent than unloaded curcumin and curcumin loaded in SEDDS without the glyceryl ester surfactants.

CONCLUSIONS

Glyceryl ester surfactants and in particular polyglyceryl-3-stearate might be a promising excipient for the formulation of SEDDS exhibiting enhanced cellular uptake and permeation enhancing properties.