Tumor regression after intravenous administration of targeted vesicles entrapping the vitamin E α-tocotrienol

Karim, Reatul and Somani, Sukrut and Al Robaian, Majed and Mullin, Margaret and Amor, Rumelo and McConnell, Gail and Dufès, Christine (2017) Tumor regression after intravenous administration of targeted vesicles entrapping the vitamin E α-tocotrienol. Journal of Controlled Release, 246. pp. 79-87. ISSN 0168-3659

[img]
Preview
Text (Karim-etal-JCR2017-Tumor-regression-after-intravenous-administration-of-targeted-vesicles)
Karim_etal_JCR2017_Tumor_regression_after_intravenous_administration_of_targeted_vesicles.pdf
Accepted Author Manuscript
License: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 logo

Download (703kB)| Preview

    Abstract

    The therapeutic potential of tocotrienol, a member of the vitamin E family of compounds with potent in vitro anti-cancer properties, is limited by its inability to specifically reach tumors following intravenous administration. The purpose of this study is to determine whether a novel tumor-targeted vesicular formulation of tocotrienol would suppress the growth of A431 epidermoid carcinoma and B16-F10 melanoma in vitro and in vivo. In this work, we demonstrated that novel transferrin-bearing multilamellar vesicles entrapping α-T3 resulted in a dramatically improved (by at least 52-fold) therapeutic efficacy in vitro on A431 cell line, compared to the free drug. In addition, the intravenous administration of tocotrienol entrapped in transferrin-bearing vesicles resulted in tumor suppression for 30% of A431 and 60% of B16-F10 tumors, without visible toxicity. Mouse survival was enhanced by more than 13 days compared to controls administered with the drug solution only. This tumor-targeted, tocotrienol-based nanomedicine therefore significantly improved the therapeutic response in cancer treatment.