Tumor regression after systemic administration of tocotrienol entrapped in tumor-targeted vesicles
Fu, Ju Yen and Blatchford, David R. and Tetley, L. and Dufès, Christine (2009) Tumor regression after systemic administration of tocotrienol entrapped in tumor-targeted vesicles. Journal of Controlled Release, 140 (2). pp. 95-99. ISSN 0168-3659 (https://doi.org/10.1016/j.jconrel.2009.08.017)
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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.
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Item type: Article ID code: 15271 Dates: DateEvent3 December 2009PublishedSubjects: Medicine > Pharmacy and materia medica
Medicine > Therapeutics. Pharmacology
Science > MicrobiologyDepartment: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences Depositing user: Ms Ann Barker-Myles Date deposited: 08 Jan 2010 18:09 Last modified: 08 Apr 2024 17:15 URI: https://strathprints.strath.ac.uk/id/eprint/15271