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

J Control Release. 2017 Jan 28:246:79-87. doi: 10.1016/j.jconrel.2016.12.014. Epub 2016 Dec 18.

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 >13days compared to controls administered with the drug solution only. This tumor-targeted, tocotrienol-based nanomedicine therefore significantly improved the therapeutic response in cancer treatment.

Keywords: Cancer therapy; Delivery system; Tocotrienol; Transferrin; Tumor targeting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravenous
  • Animals
  • Antioxidants / administration & dosage*
  • Antioxidants / therapeutic use
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Drug Carriers / metabolism
  • Drug Delivery Systems*
  • Female
  • Humans
  • Melanoma, Experimental / drug therapy*
  • Melanoma, Experimental / metabolism
  • Melanoma, Experimental / pathology
  • Mice
  • Mice, Inbred BALB C
  • Tocotrienols / administration & dosage*
  • Tocotrienols / therapeutic use
  • Transferrin / metabolism

Substances

  • Antioxidants
  • Drug Carriers
  • Tocotrienols
  • Transferrin
  • tocotrienol, alpha