A new formulation of the vitamin E extract tocotrienol could play a key role in treating cancerous tumors without harming healthy tissue. Tocotrienol has anti-cancer properties, but when given intravenously it has secondary effects on healthy tissue; now researchers in the UK have found that delivering the compound encapsulated in transferrin-bearing vesicles can shrink tumors without causing visible toxic effects.

A study of the work, by researchers at the University of Glasgow and the University of Strathclyde, is published in the 3 December issue of the Journal of Controlled Release. Dr Christine Dufès, a Lecturer at the Strathclyde Institute of Pharmacy and Biomedical Sciences, led the research.

Dufès and colleagues wrote that previous attempts to use the vitamin E extract tocotrienol to shrink tumors found that while it has the requisite anti-cancer properties, it failed to reach tumors after intravenous administration without secondary effects to healthy tissues.

“In the anti-cancer studies done to date, no therapeutic effect has been found after intravenous administration of tocotrienol,” said Dufès.

So she and her colleagues hypothesized that if they could encapsulate “a tocotrienol-rich fraction (TRF) within vesicles bearing transferrin”, they could perhaps selectively deliver it to tumors.

Transferrin is a plasma protein that carries iron in the blood and whose receptors can be found in large amounts in many cancers.

The researchers tested their hypothesis in test tube (in vitro) and live animal (in vivo) experiments and found that:

  • “The entrapment of TRF in transferrin-bearing vesicles led to a 3-fold higher TRF uptake and more than 100-fold improved cytotoxicity in A431 (epidermoid carcinoma), T98G (glioblastoma) and A2780 (ovarian carcinoma) cell lines compared to TRF solution,” wrote the authors.

  • Compared to controls, intravenous administration of TRF encapsulated in transferrin-bearing vesicles in mice with led to tumor regression and improvement of animal survival.

  • The treatment was well tolerated by the mice.

Delivering TRF in this manner led to tumors shrinking within one day of treatment: and by the tenth day, the maximum duration allowed for the experiment, they had nearly disappeared altogether, and although they started growing again after the end of the treatment, the rate of growth was slower than in previous trials using other formulations, the researchers told the press.

Dufès and colleagues concluded that the study was the ” first preparation of a tumor-targeted delivery system able to encapsulate tocotrienol”, and shows that:

“TRF encapsulated in transferrin-bearing vesicles is a highly promising therapeutic system, leading to tumor regression after intravenous administration without visible toxicity.”

Dufès told the press that they were very encouraged by the results.

“We demonstrated that the intravenous administration of tocotrienol entrapped in a tumor-targeted delivery system leads to a fast tumour regression without visible secondary effects on healthy tissues.”

She and her team are hoping to further improve the therapeutic efficacy of the system by testing higher doses and extending the length of treatment.

“This therapeutic system is very promising. We have tested it in laboratory settings on skin cancer and are currently investigating other therapeutic systems which give promising results as well,” said Dufès.

“Tumor regression after systemic administration of tocotrienol entrapped in tumor-targeted vesicles.”
Journal of Controlled Release, Volume 140, Issue 2, 3 December 2009, Pages 95-99.
Ju Yen Fu, David R. Blatchford, Laurence Tetley, Christine Dufès.
DOI:10.1016/j.jconrel.2009.08.017

Source: University of Glasgow.

Written by: Catharine Paddock, PhD