Vitamin E-based micelles enhance the anticancer activity of doxorubicin

• Published in: International journal of pharmaceutics Vol. 476; no. 1-2; pp. 9 - 15
• Main Authors: Danhier, Fabienne, Kouhé, Trésor Touan Bi, Duhem, Nicolas, Ucakar, Bernard, Staub, Aurélie, Draoui, Nihed, Feron, Olivier, Préat, Véronique
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 10.12.2014
• Subjects: alpha-Tocopherol - chemistry; Animals; Anti-cancer drug delivery; Antibiotics, Antineoplastic - administration & dosage; Antibiotics, Antineoplastic - pharmacology; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cell Line, Tumor; Colonic Neoplasms - drug therapy; Colonic Neoplasms - pathology; Doxorubicin; Doxorubicin - administration & dosage; Doxorubicin - pharmacology; Drug Delivery Systems; Excipients - chemistry; Female; Humans; Inhibitory Concentration 50; MCF-7 Cells; Mice; Mice, Nude; Micelles; Nanomedicines; Polyethylene Glycols - chemistry; Survival Rate; Vitamin E - analogs & derivatives; Vitamin E - chemistry; Vitamin E derivatives; Vitamin E derivatives; Anti-cancer drug delivery; Doxorubicin; Micelles; Nanomedicines
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2014.09.028

[Display omitted] The purpose of this study was to develop vitamin E-based micelles loaded with Doxorubicin (DOX) (DOX–TOS–TPGS), taking advantages of the anti-cancer activity of vitamin E derivatives: Tocopherol succinate (TOS) and d-α-tocopherol polyethylene2000 succinate (TPGS). Therefore, we developed micelles consisting in a mixture of TOS (as solubilizer) and TPGS2000 (as stabilizer) (1:1). DOX–TOS–TPGS micelles exhibited a size of 78nm and a ζ potential of −7mV. High drug loading (40% w/w) was achieved. The critical micellar concentration was determined at 14μg/ml. In vitro, after 24h, DOX-TOS- TPGS micelles exhibited higher cytotoxicity than free-DOX (IC50 on MCF-7 cells, at 24h, 58 vs 5μg/ml). In vivo anti-tumor efficacy, performed on two tumor models (CT26 and MCF-7), demonstrated a 100% long-term survival of mice when treated with DOX–TOS–TPGS compared to DOX-free. Interestingly, the survival time of mice treated with unloaded TOS–TPGS micelles was similar to DOX-free, indicating an anti-cancer activity of vitamin E derivatives. Based on these results, it can be concluded that the formulations developed in this work may be considered as an effective DOX delivery system for cancer chemotherapy.