Doxorubicin and curcumin co-delivery by lipid nanoparticles for enhanced treatment of diethylnitrosamine-induced hepatocellular carcinoma in mice

European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V
Xiaojing ZhaoXiangliang Yang

Abstract

At present, the treatment of hepatocellular carcinoma (HCC) is an international problem. The delivery of a chemotherapeutic agent and chemosensitizer using nanocarriers has been suggested as a novel and promising strategy in cancer treatment. However, such studies in HCC remain very limited. In this study, we developed doxorubicin (DOX) and curcumin (Cur) co-delivery lipid nanoparticles (DOX/Cur-NPs) and examined its inhibitory effect on diethylnitrosamine (DEN)-induced HCC in mice. DOX/Cur-NPs displayed the physicochemical characterizations with uniform particle size, high encapsulation efficacy and sustained release profile. In DNE-induced HCC mice treated with DOX/Cur-NPs, we observed decreased liver damage assessed by serum ALT and AST levels, liver/body weight ratio, and histopathological analysis. Compared with DOX-loaded nanoparticles (DOX-NPs), DOX/Cur-NPs induced increased Caspase-3 and Bax/Bcl-2 ratio, and decreased C-myc, PCNA and VEGF. The results revealed the synergistic effect of DOX/Cur-NPs on the apoptosis, proliferation and angiogenesis of HCC. The mRNA levels of MDR1, bcl-2 and HIF-1α, and protein levels of P-gp, Bcl-2 and HIF-1α were decreased in DOX/Cur-NPs than those in DOX-NPs, indicating that Cur might re...Continue Reading

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Citations

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