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https://tkuir.lib.tku.edu.tw/dspace/handle/987654321/119677
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| 题名: | Surface-functionalized layered double hydroxide nanocontainers as bile acid sequestrants for lowering hyperlipidemia |
| 作者: | Lin, Chiao-Wen;Lin, Shi-Xiang;Kankala, Ranjith Kumar;Busa, Prabhakar;Deng, Jin-Pei;Lue, Sheng-I;Liu, Chen-Lun;Weng, Ching-Feng;Lee, Chia-Hung |
| 关键词: | Bile acid sequestrants;Two-dimensional;Cholesterol;Layered double hydroxides;Nanoparticles |
| 日期: | 2020-11-30 |
| 上传时间: | 2020-12-02 12:10:17 (UTC+8) |
| 出版者: | Elsevier |
| 摘要: | The surface modification of two-dimensional (2D) nanocontainers with versatile chemical functionalities offers enormous advantages in medicine owing to their altered physicochemical properties. In this study, we demonstrate the fabrication of surface-functionalized layered double hydroxides (LDHs) towards their use as effective intestinal bile acid sequestrants. To demonstrate these aspects, the LDHs are initially modified with an amino silane, N1-(3-trimethoxysilylpropyl) diethylenetriamine (LDHs-N3), which, on the one hand, subsequently used for the fabrication of the dendrimer by repetitive immobilization of ethylene diamine using methyl acrylate as a spacer. On the other hand, these surface-functionalized LDHs are wrapped with an anionic enteric co-polymer to not only prevent the degradation but also increase the stability of these 2D nanoplates in an acidic environment of the stomach to explore the in vivo efficacy. In vitro cholic acid adsorption results showed that these surface-functionalized LDHs displayed tremendous adsorption ability of bile salt. Consequently, the bile salt adsorption results in vivo in mice confirmed that the enteric polymer-coated diethylenetriamine silane-modified LDHs, resulting in the reduced cholesterol by 8.2% in the high fat diet-fed mice compared to that of the oil treatment group with augmented 28% of cholesterol, which gained weight by 6.7% in 4 weeks. Notably, the relative organ (liver and kidney) weight analysis and the tissue section of histology results indicated that the modified LDHs showed high biocompatibility in vivo. Together, our findings validate that these surface-functionalized 2D nanoplates have great potential as effective intestinal bile acid sequestrants. |
| 關聯: | International Journal of Pharmaceutics 590, 119921 |
| DOI: | 10.1016/j.ijpharm.2020.119921 |
| 显示于类别: | [化學學系暨研究所] 期刊論文
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