Formulation and Investigation of Specialised Dosage Forms for the Systematic Delivery of the Selective Antineoplastic a-Tocopheryl Succinate

Abstract

Background. a-Tocopheryl succinate, a redox-silent analogue of vitamin E, has been shown to selectively induce apoptosis in a variety of cancers. However, a-tocopheryl succinate is rendered ineffective when administered orally due to hepatic metabolism. Transdermal delivery has been identified as an alternative approach for delivering in-tact a-tocopheryl succinate systemically. Aims and objectives. The aim of this study was to compound a liposomal formulation of a-tocopheryl succinate and evaluate the transdermal diffusion in an in-vitro Franz diffusion cell assay. The feasibility of transdermal delivery was further evaluated by studying the potential metabolism of a-tocopheryl succinate by esterases, which are commonly located in the skin. Methods. Large quantities of a-tocopheryl succinate was sourced and characterised by nuclear magnetic resonance, mass spectrometry, infrared spectroscopy and differential scanning calorimetry for the compounding of transdermal dosage forms. Analytical high performance liquid chromatography and extraction methods were developed and validated to isolate, identify and quantify a-tocopheryl succinate.