Artículo
Antitumor efficacy and cardiotoxic effect of doxorubicin-loaded mixed micelles in 4T1 murine breast cancer model: Comparative studies using Doxil® and free doxorubicin
Cagel, Carlos Maximiliano
; Moretton, Marcela Analía
; Bernabeu, Ezequiel Adrian
; Zubillaga, Marcela Beatriz
; Lagomarsino, Eduardo; Vanzulli, Silvia; Nicoud, Melisa Beatriz
; Medina, Vanina Araceli
; Salgueiro, María Jimena; Chiappetta, Diego Andrés
Fecha de publicación:
04/2020
Editorial:
Editions Sante
Revista:
Journal of Drug Delivery Science and Technology
ISSN:
1773-2247
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Doxorubicin-loaded mixed micelles (DOX-micelles) were formulated employing TPGS and a poloxamine (Tetronic® T1107) in order to investigate their pharmaceutical application as an alternative anticancer nanotherapy. DOX-micelles presented unimodal behaviour, exhibiting average size values of 10.7 ± 0.2 nm and 10.4 ± 0.1 nm, before and after lyophilization, respectively. The in vitro cytotoxic effect of DOX-micelles was significantly higher (p < 0.05) than Doxil® on 4T1 murine breast cancer cells. The in vitro cell-based internalization assays showed a significant augment (p < 0.05) of the intracellular DOX content for the DOX-micelles in comparison to the liposomes and free DOX in these 4T1 cells at 2 and 6 h. Besides, DOX-micelles presented higher in vivo anticancer effect than Doxil® and equivalent potency to the free drug. Moreover, the in vivo histopathological toxicity studies revealed that the DOX-micelles produced significant less cardiac damage than free DOX, while the in vivo immunohistochemical assays exhibited a significantly higher DNA damage in the cardiac tissue with the free DOX than with our DOX-micelles. All these results demonstrate that our novel nanotechnological platform could successfully deliver DOX to the tumor with reduced cardiotoxicity, thus showing promising clinical potential as an anticancer drug delivery carrier.
Palabras clave:
4T1 BREAST CANCER MODEL
,
DOXIL®
,
DOXORUBICIN
,
MIXED MICELLES
,
TPGS
Archivos asociados
Licencia
Identificadores
Colecciones
Articulos(BIOMED)
Articulos de INSTITUTO DE INVESTIGACIONES BIOMEDICAS
Articulos de INSTITUTO DE INVESTIGACIONES BIOMEDICAS
Articulos(OCA HOUSSAY)
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Citación
Cagel, Carlos Maximiliano; Moretton, Marcela Analía; Bernabeu, Ezequiel Adrian; Zubillaga, Marcela Beatriz; Lagomarsino, Eduardo; et al.; Antitumor efficacy and cardiotoxic effect of doxorubicin-loaded mixed micelles in 4T1 murine breast cancer model: Comparative studies using Doxil® and free doxorubicin; Editions Sante; Journal of Drug Delivery Science and Technology; 56; 4-2020; 1-10
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