Fu, J.Y., Blatchford, D.R., Tetley, L. and Dufès, C. (2009) Tumor regression after systemic administration of tocotrienol entrapped in tumor-targeted vesicles. Journal of Controlled Release, 140(2), pp. 95-99. (doi: 10.1016/j.jconrel.2009.08.017)
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Abstract
The therapeutic potential of tocotrienol, an extract of vitamin E with anti-cancer properties, is hampered by its failure to specifically reach tumors after intravenous administration, without secondary effects on normal tissues. We hypothesize that the encapsulation of tocotrienol-rich fraction (TRF) within vesicles bearing transferrin, whose receptors are overexpressed on many cancer cells, could result in a selective delivery to tumors after intravenous administration. The objectives of this study are therefore to prepare and characterize transferrin-targeted vesicles encapsulating TRF, and to evaluate their therapeutic efficacy in vitro and in vivo. 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. The intravenous administration of TRF encapsulated in transferrin-bearing vesicles led to tumor regression and improvement of animal survival in a murine xenograft model, contrary to that observed with controls. The treatment was well tolerated by the animals. This work corresponds to the first preparation of a tumor-targeted delivery system able to encapsulate tocotrienol. Our findings show that TRF encapsulated in transferrin-bearing vesicles is a highly promising therapeutic system, leading to tumor regression after intravenous administration without visible toxicity.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Tetley, Dr Laurence |
| Authors: | Fu, J.Y., Blatchford, D.R., Tetley, L., and Dufès, C. |
| Subjects: | R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) Q Science > QH Natural history > QH301 Biology |
| College/School: | College of Medical Veterinary and Life Sciences > School of Life Sciences |
| Journal Name: | Journal of Controlled Release |
| ISSN: | 0168-3659 |
| ISSN (Online): | 1873-4995 |
| Published Online: | 23 August 2009 |
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