Abstract
Vitamin E refers to a family of eight isomers divided into two subgroups, tocopherols and the therapeutically active tocotrienols (T-3). The PEGylated a-tocopherol isomer of vitamin E (vitamin E TPG5) has been extensively investigated for its solubilizing capacity as a nonionic surfactant in various drug delivery systems. Limited information, however, is available about the PEG conjugates of the tocotrienol isomers of vitamin E. In this study two PEGylated gamma-T-3 variants with mPEG molecular weights of 350 (gamma-T(3)PGS 350) and 1000 (7-T3PGS 1000) were synthesized by a two-step reaction procedure and characterized by H-1 NMR, HPLC, and mass spectroscopy. The physical properties of their self-assemblies in water were characterized by zeta, CMC, and size analysis. Similar physical properties were found between the PEGylated T-3 and vitamin E TPGS. PEGylated T-3 were also found to retain the in vitro cytotoxic activity of the free T3 against the MCF-7 and the triple-negative MDA-MB-231 breast cancer cells. PEGylated gamma-T-3 also increased the oral bioavailability of gamma-T-3 by threefolds when compared to the bioavailability of gamma-T-3 formulated into a self-emulsified drug delivery system. No significant differences in biological activity were found between the PEG 350 and 100 conjugates. Results from this study suggest that PEGylation of gamma-T-3 represents a viable platform for the oral and parenteral delivery of gamma-T-3 for potential use in the prevention of breast cancer. (C) 2015 Elsevier B.V. All rights reserved.