Lyophilised liposome-based formulations of alpha-tocopheryl succinate: preparation and physico-chemical...

alpha-Tocopheryl succinate (alpha-TOS) is a semisynthetic analogue of alpha-tocopherol with selective toxicity to the cancer cells and anticancer activity in vivo. Yet, no suitable formulation of alpha-TOS for medical application has been reported. Various formulations, for example, solutions in organic solvents, oil emulsions and vesicules prepared by spontaneous vesiculation, polyethylene glycol conjugates and liposomes of various compositions have been tested. We developed and characterised a stable lyophilised liposome-based alpha-TOS formulation. alpha-TOS (15 mol%) was incorporated into large oligolamellar vesicles (OLVs) composed of soy phosphatidylcholine (SPC) by the method of lipid film hydration followed by extrusion through polycarbonate filters. Stabilised liposomal formulation was prepared by lyophilisation in the presence of sucrose (molar ratio lipid/sucrose, 1:5). The size distribution of the liposomes (130-140 nm, polydispersity index 0.14) as well as the stable lipid and alpha-TOS contents were preserved during storage in the lyophilised form at 2-8 degrees C for at least 6 months. The data indicate good physical and chemical stability of the lyophilised preparation of alpha-TOS liposomes that can be used in clinical medicine.