Liposomal formulation of alpha-tocopheryl maleamide: In vitro and in vivo toxicological profile and anticancer effect against spontaneous breast carcinomas in mice

0340455 - BTÚ 2010 RIV US eng J - Článek v odborném periodiku
Turánek, J. - Wang, X. F. - Knötigová, P. - Koudelka, Š. - Dong, L. F. - Vrublová, E. - Mahdavian, E. - Procházka, L. - Sangsura, S. - Vacek, A. - Salvatore, B. A. - Neužil, Jiří
Liposomal formulation of alpha-tocopheryl maleamide: In vitro and in vivo toxicological profile and anticancer effect against spontaneous breast carcinomas in mice.
Toxicology and Applied Pharmacology. Roč. 237, č. 3 (2009), s. 249-257. ISSN 0041-008X. E-ISSN 1096-0333
Grant CEP: GA AV ČR KAN200520703; GA AV ČR(CZ) IAA500520602
Výzkumný záměr: CEZ:AV0Z50520701
Klíčová slova: Liposome * apoptosis * vitamin E analogues
Kód oboru RIV: FR - Farmakologie a lékárnická chemie
Impakt faktor: 3.359, rok: 2009

The vitamin E analogue α-tocopheryl succinate (α-TOS) is an efficient anti-cancer drug. Improved efficacy was achieved through the synthesis of an esterase-resistant α-tocopheryl maleamide (α-TAM). In vitro tests demonstrated higher cytotoxicity of α-TAM towards cancer cells (MCF-7, B16F10) compared to α-TOS prone to esterase-catalyzed hydrolysis. We developed lyophilized liposomal formulations of both α-TOS and α-TAM to solve the problem with cytotoxicity of free α-TAM, as well as the low solubility of both drugs. Neither acute toxicity nor immunotoxicity implicated by in vitro tests was detected in vivo after application of liposomal α-TAM, which significantly reduced the growth of cancer cells in hollow fiber implants. Moreover, liposomal formulation of α-TAM and α-TOS each prevented the growth of tumours in transgenic FVB/N c-neu mice bearing spontaneous breast carcinomas. Liposomal formulation of α-TAM demonstrated anti-cancer activity at levels 10-fold lower than those of α-TOS.
Trvalý link: http://hdl.handle.net/11104/0183680