octanoyl galactose ester-modified microemulsion system self-assembled by coix seed components to enhance tumor targeting and hepatoma therapy
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2017
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Abstract
Ding Qu,1,2 Mingjian Liu,1 Mengmeng Huang,1,2 Lixiang Wang,1 Yan Chen,1,2 Congyan Liu,1,2 Yuping Liu1,2 1Research Center for Multicomponent Traditional Medicine and Microecology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 2Research Center for Multicomponent Traditional Medicine and Microecology, Jiangsu Provincial Academy of Traditional Chinese Medicine, Nanjing, People’s Republic of China Abstract: A nanosized drug delivery platform with a combination of rational components and tumor targeting is significant for enhancement of anticancer therapy and reduction of side effects. In this study, we developed a octanoyl galactose ester-modified microemulsion system self-assembled by coix seed components (Gal(oct)-C-MEs), which improved the tumor accumulation through asialoglycoprotein receptor-mediated endocytosis and promoted the antitumor efficacy through multicomponent-mediated synergistic effect. Octanoyl galactose ester (Gal(oct)) with a yield of 82.3% was synthesized through a green enzymatic reaction and multidimensional characterization. Gal(oct)-C-MEs with a spherical shape had a small and uniform particle size (58.49±1.03 nm), narrow polydispersity index (0.09±0.01) and neutral surface charge (-5.82±0.57 mV). In the cellular uptake studies, the internalized Gal(oct)-C-ME was 2.28-fold higher relative to that of coix seed component-based microemulsions (C-MEs). The half-maximal inhibitory concentration of Gal(oct)-C-MEs against HepG2 cells was 46.5±2.4 µg/mL, which was notably higher than that of C-MEs. Importantly, the intratumor fluorescence of HepG2 xenograft-bearing nude mice treated with Cy5/Gal(oct)-C-MEs was 1.9-fold higher relative to treatment with Cy5/C-MEs. In the study of antitumor efficacy in vivo, HepG2 xenograft-bearing nude mice intragastrically administered Gal(oct)-C-MEs for 14 days exhibited the strongest inhibition of tumor growth and the lowest toxicity against liver and kidney among all the treatments. In summary, Gal(oct)-C-ME, as a highly effective and safe anticancer drug delivery system, showed promising potential for hepatoma therapy. Keywords: coix seed oil, coixan, multicomponent-based microemulsion, hepatic targeting, antihepatoma, oral drug delivery system
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d2017internationaloctanoyl
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| Authors | ;Qu D;Liu M;Huang M;Wang L;Chen Y;Liu C;Liu Y |
| Journal | nonlinear analysis: real world applications |
| Year | 2017 |
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