Self-emulsifying drug delivery systems and cationic surfactants: do they potentiate each other in cytotoxicity?

Abstract

The aim of this study was to evaluate the cytotoxicity of self-emulsifying drug delivery systems (SEDDS) containing five different cationic surfactants. Cationic surfactants were added in a concentration of 1% and 5% (m/m) to SEDDS comprising 30% Capmul MCM, 30% Captex 355, 30% Cremophor EL and 10% propylene glycol. The resulting formulations were characterized in terms of size, zeta potential, in-vitro haemolytic activity and toxicity on Caco-2 via MTT assay and lactate dehydrogenase release assay. The evaluated surfactants had in both concentrations a minor impact on the size of SEDDS ranging from 30.2±0.6 to 55.4±1.1nm, whereas zeta potential changed significantly from -9.0±0.3 to +28.8±1.6mV. The overall cytotoxicity of cationic surfactants followed the rank order: hexadecylpyridinium chloride>benzalkonium chloride>alkyltrimethylammonium bromide>octylamine>1-decyl-3-methylimidazolium. The haemolytic activity of the combination of cationic surfactants and SEDDS on human red blood cells was synergistic. Furthermore, cationic SEDDS exhibited higher cytotoxicity of Caco-2 cells compared to SEDDS without cationic surfactants. According to these results, SEDDS and cationic surfactants seem to bear an additive up to synergistic toxic risk.