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Pharm Dev Technol ; 25(7): 865-873, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32266855

RESUMEN

Fenretinide (4-HPR), as a semi-synthetic retinoid, has apoptosis-promoting effects as a single agent and chemotherapy synergist in vitro. When a human ovarian cancer cells line (A2780s) was treated with both PTX and 4-HPR, there was a synergistic anti-cancer effect demonstrated with a average combination index of 0.44. In this research, a new TPGS-Soluplus® mixed micelles were developed which encapsulation efficiencies of paclitaxel (PTX) and fenretinide (4-HPR) were as high as 98%, and the average diameter of the micelles was 66.26 nm. Cytotoxicity of the mixed micelles co-delivered with PTX and 4-HPR reduced significantly 7.3 and 25.1 times compared with free drug respectively in A2780s cells. More importantly, in vivo pharmacokinetic study, the loaded drugs in mixed micelles exhibited higher AUC and t1/2 values than free drugs. Furthermore, in vivo antitumor efficacy experiments demonstrated that PF-TS exhibited superior in vivo antitumor activity on the inhibition rate of tumor growth than other treatment groups (77.8% corresponding tumor growth inhibition in PF-TS treated group vs 19.9, 12.5, and 26.0% of tumor growth inhibition rate in Taxol®, 4-HPR, and Taxol®+4-HPR, respectively). Therefore, the mixed micelles of co-deliver PTX and 4-HPR successfully constructed may hopefully be applied to the cancer combination treatment with less toxic effect and more antitumor activity.


Asunto(s)
Antineoplásicos/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Fenretinida/administración & dosificación , Micelas , Paclitaxel/administración & dosificación , Polietilenglicoles/administración & dosificación , Polivinilos/administración & dosificación , Vitamina E/administración & dosificación , Animales , Antineoplásicos/farmacocinética , Línea Celular Tumoral , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/farmacocinética , Femenino , Fenretinida/farmacocinética , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Paclitaxel/farmacocinética , Polietilenglicoles/farmacocinética , Polivinilos/farmacocinética , Ratas , Ratas Wistar , Carga Tumoral/efectos de los fármacos , Carga Tumoral/fisiología , Vitamina E/farmacocinética , Ensayos Antitumor por Modelo de Xenoinjerto/métodos
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