title: Vitamin E-based micelles enhance the anticancer activity of doxorubicin.
abstract: 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 78 nm and a ζ potential of -7 mV. High drug loading (40% w/w) was achieved. The critical micellar concentration was determined at 14 μg/ml. In vitro, after 24 h, DOX-TOS-TPGS micelles exhibited higher cytotoxicity than free-DOX (IC50 on MCF-7 cells, at 24 h, 58 vs 5 μg/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.
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Avenue Mounier 73 bte B1 73.12, B-1200 Brussels, Belgium.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Danhier
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Avenue Mounier 73 bte B1 73.12, B-1200 Brussels, Belgium.
authors.forename: Trésor Touan Bi
authors.initials: TT
authors.lastname: Kouhé
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Avenue Mounier 73 bte B1 73.12, B-1200 Brussels, Belgium.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Duhem
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Avenue Mounier 73 bte B1 73.12, B-1200 Brussels, Belgium.
authors.forename: Bernard
authors.initials: B
authors.lastname: Ucakar
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Avenue Mounier 73 bte B1 73.12, B-1200 Brussels, Belgium.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Staub
authors.affiliation: Université catholique de Louvain, Institut de recherche expérimentale et Clinique, Pôle de Pharmacologie et thérapeutique, Avenue Mounier 53 bte B1.53.09, B-1200 Brussels, Belgium.
authors.forename: Nihed
authors.initials: N
authors.lastname: Draoui
authors.affiliation: Université catholique de Louvain, Institut de recherche expérimentale et Clinique, Pôle de Pharmacologie et thérapeutique, Avenue Mounier 53 bte B1.53.09, B-1200 Brussels, Belgium.
authors.forename: Olivier
authors.initials: O
authors.lastname: Feron
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Avenue Mounier 73 bte B1 73.12, B-1200 Brussels, Belgium. Electronic address: veronique.preat@uclouvain.be.
authors.forename: Véronique
authors.initials: V
authors.lastname: Préat
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology*; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D051379:Mice; D008819:Mice, Nude; D008823:Micelles; D011092:Polyethylene Glycols / Q000737:chemistry; D015996:Survival Rate; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000737:chemistry; D024502:alpha-Tocopherol / Q000737:chemistry
chemical_list: D000903:Antibiotics, Antineoplastic; D005079:Excipients; D008823:Micelles; D014810:Vitamin E; D011092:Polyethylene Glycols; D004317:Doxorubicin; D024502:alpha-Tocopherol; C014225:tocophersolan
keywords: Anti-cancer drug delivery; Doxorubicin; Micelles; Nanomedicines; Vitamin E derivatives