Artículo
Mixed micelles for encapsulation of doxorubicin with enhanced in vitro cytotoxicity on breast and ovarian cancer cell lines versus Doxil®
Cagel, Carlos Maximiliano
; Bernabeu, Ezequiel Adrian
; Gonzalez, Lorena; Lagomarsino, Eduardo; Zubillaga, Marcela Beatriz
; Moretton, Marcela Analía
; Chiappetta, Diego Andrés
Fecha de publicación:
11/2017
Editorial:
Elsevier France-editions Scientifiques Medicales Elsevier
Revista:
Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
ISSN:
0753-3322
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Doxorubicin (DOX) is used as a “first-line” antineoplastic drug in ovarian and metastatic breast cancer. However, serious side effects, such as cardiotoxicity have been reported after DOX intravenous administration. Hence, we investigated different micelle-former biomaterials, as Soluplus®, Pluronic F127, Tetronic T1107 and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) to develop a potential mixed micellar nanocarrier for DOX delivery. Since DOX hydrochloride is a poor candidate to be encapsulated inside the hydrophobic core of the mixed micelles, we assayed a hydrophobic complex between DOX and sodium deoxycholate (NaDC) as an excellent candidate to be encapsulated within polymeric micelles. The combination of T1107:TPGS (1:3, weight ratio) demonstrated the best physicochemical properties together with a high DL capacity (6.43% w/v). Particularly, DOX in vitro release was higher at acidic tumour microenvironment pH value (5.5) than at physiological counterpart (7.4). The hydrodynamic diameter of the DOX/NaDC-loaded mixed micellar system was 10.7 nm (PDI = 0.239). The in vitro cytotoxicity of the mixed micellar formulation resulted significantly (p < 0.05) higher than Doxil® against ovarian (SKOV-3) and triple-negative breast cancer cells (MDA-MB- 231). Further, the in vitro cellular uptake assays demonstrated a significant increment (p < 0.05) of the DOX intracellular content for the mixed micelles versus Doxil® for both, SKOV-3 (at 2, 4 and 6 h of incubation) and MDA-MB-231 (at 4 h of incubation) cells. These findings suggest that T1107:TPGS (1:3) mixed micelles could be employed as a potential nanotechnological platform for drug delivery of DOX.
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Articulos(OCA HOUSSAY)
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Citación
Cagel, Carlos Maximiliano; Bernabeu, Ezequiel Adrian; Gonzalez, Lorena; Lagomarsino, Eduardo; Zubillaga, Marcela Beatriz; et al.; Mixed micelles for encapsulation of doxorubicin with enhanced in vitro cytotoxicity on breast and ovarian cancer cell lines versus Doxil®; Elsevier France-editions Scientifiques Medicales Elsevier; Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie; 95; 11-2017; 894-903
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