Novel tocotrienol-entrapping vesicles can eradicate solid tumors after intravenous administration

Fu, J.Y. and Zhang, Wei and Blatchford, David and Tetley, Laurence and Mcconnell, Gail and Dufès, Christine (2011) Novel tocotrienol-entrapping vesicles can eradicate solid tumors after intravenous administration. Journal of Controlled Release, 154 (1). pp. 20-26. ISSN 0168-3659

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Abstract

The therapeutic potential of tocotrienol, a vitamin E extract with anti-cancer properties, is hampered by its failure to specifically reach tumors after intravenous administration. In this work, we demonstrated that novel transferrin-bearing, tocopheryl-based multilamellar vesicles entrapping tocotrienol significantly improved tocotrienol uptake by cancer cells overexpressing transferrin receptors. This led to a dramatically improved therapeutic efficacy in vitro, ranging from 17-fold to 72-fold improvement depending on the cell lines, compared to the free drug. In vivo, the intravenous administration of this novel tocotrienol formulation led to complete tumor eradication for 40% of B16F10 murine melanoma tumors and 20% of A431 human epidermoid carcinoma tumors. Animal survival was improved by more than 20 days compared to controls, for the two tumor models tested. These therapeutic effects, together with the lack of toxicity, potentially make transferrin-bearing vesicles entrapping tocotrienol a highly promising therapeutic system as part as an anti-cancer therapeutic strategy.