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

J.Y. Fu, Wei Zhang, David Blatchford, Laurence Tetley, Gail Mcconnell, Christine Dufès

Research output: Contribution to journalArticle

  • 15 Citations

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.
LanguageEnglish
Pages20-26
Number of pages7
JournalJournal of Controlled Release
Volume154
Issue number1
Early online date22 Apr 2011
DOIs
StatePublished - 25 Aug 2011

Fingerprint

Tocotrienols
Intravenous Administration
Neoplasms
Transferrin
Transferrin Receptors
Therapeutic Uses
Therapeutics
Vitamin E
Squamous Cell Carcinoma
Melanoma
Cell Line

Keywords

  • tocotrienol
  • cancer therapy
  • delivery system
  • tumor targeting
  • transferring

Cite this

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title = "Novel tocotrienol-entrapping vesicles can eradicate solid tumors after intravenous administration",
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.",
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Novel tocotrienol-entrapping vesicles can eradicate solid tumors after intravenous administration. / Fu, J.Y.; Zhang, Wei; Blatchford, David; Tetley, Laurence; Mcconnell, Gail; Dufès, Christine.

In: Journal of Controlled Release, Vol. 154, No. 1, 25.08.2011, p. 20-26.

Research output: Contribution to journalArticle

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AB - 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.

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