Tocopheryl polyethylene glycol 1000 succinate (TPGS-1000) in ophthalmic liposomal formulations: friend or foe?

Tocopheryl polyethylene glycol 1000 succinate (TPGS-1000) is a nonionic surfactant commonly used in pharmaceutical formulation as solubilizer, emulsifier and permeation enhancer. The aim of this study was to assess the impact of TPGS-1000 incorporation on liposomal formulation characteristics, and its applicability in ophthalmic nanoformulations. To this end, liposomal formulations containing a fixed concentration of soybean phosphatidylcholine (SPC, 100 mM) with increasing concentration of TPGS-1000 (0, 0.5 and 12.5 mM) were developed by the thin lipid film hydration method, followed by extrusion. Their characterization included measurements of pH, osmolality, mean diameter, polydispersity index, zeta potential, concentration of liposomes, and morphological observation by transmission electron microscopy. In vitro cytotoxicity of SPC, TPGS-1000 and liposomal formulations was assessed on corneal epithelial cells (HCE-T) and retinal epithelial cells (ARPE-19). As an inhibitor of mitochondrial respiratory complex II, TPGS-1000 ability to induce oxidative stress was evaluated in vitro on ARPE-19 cells. The quality of the liposomal formulations improved with TPGS-1000 content, which reduced and homogenized the liposomes size, and increased the formulations translucency. However, TPGS-1000 had a dose-dependent in vitro cytotoxicity on corneal and retinal cells. The in vitro cytotoxicity of the liposomal formulations increased with TPGS-1000 content. In the presence of an antioxidant agent, the cytotoxic effect of TPGS-1000 on ARPE-19 cells was significantly decreased. Low doses of TPGS-1000 or its combination with an antioxidant should therefore be considered in ophthalmic nanoformulations, especially those targeting the posterior segment of the eye, to prevent ocular damages due to the pro-oxidant effect of TPGS-1000.