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制备具有三维有序大孔结构的新型明胶以调节难溶性药物的释放

Preparation of a Novel Form of Gelatin With a Three-Dimensional Ordered Macroporous Structure to Regulate the Release of Poorly Water-Soluble Drugs.

作者信息

Xu Jie, Zhao Zongzhe, Hao Yanna, Zhao Ying, Qiu Yang, Jiang Jie, Yu Tong, Ji Peng, Liu Ying, Wu Chao

机构信息

Pharmacy School, Liaoning Medical University, 40 Songpo Road, Linghe District, Jinzhou, Liaoning Province 121000, China.

Pharmacy School, Liaoning Medical University, 40 Songpo Road, Linghe District, Jinzhou, Liaoning Province 121000, China.

出版信息

J Pharm Sci. 2016 Sep;105(9):2940-2948. doi: 10.1016/j.xphs.2015.12.026. Epub 2016 Feb 20.

Abstract

In this study, a novel three-dimensional ordered macroporous gelatin (3DOMG) was fabricated as a carrier for increasing the solubility of poorly water-soluble drugs, offering sustained release and a high oral bioavailability. Polymethyl methacrylate nanospheres (257 nm) were used as a colloidal plastic framework to synthesize 3DOMG. Fenofibrate (FNB) was selected as a model drug and loaded onto 3DOMG by the adsorption equilibrium method. Detailed characterization showed that the FNB absorbed onto 3DOMG was in a microcrystalline state. A fluorescence experiment and the prepared drug microcrystal network gave further information on the physical state of the drug. A degradation experiment proved that 3DOMG was readily biodegradable. In vitro release testing showed that 3DOMG increased the dissolution rate of FNB and produced a sustained release. An in vivo pharmacokinetic study confirmed that 3DOMG improved the oral bioavailability compared with that of commercial sustained-release capsules. These findings confirm that 3DOMG can be regarded as a promising carrier for an oral drug delivery system.

摘要

在本研究中,制备了一种新型的三维有序大孔明胶(3DOMG)作为载体,以提高难溶性药物的溶解度,实现药物的缓释并提高口服生物利用度。聚甲基丙烯酸甲酯纳米球(257 nm)用作胶体塑料骨架来合成3DOMG。选择非诺贝特(FNB)作为模型药物,并通过吸附平衡法将其负载到3DOMG上。详细表征表明,吸附在3DOMG上的FNB处于微晶状态。荧光实验和制备的药物微晶网络进一步提供了药物物理状态的信息。降解实验证明3DOMG易于生物降解。体外释放测试表明,3DOMG提高了FNB的溶解速率并实现了缓释。体内药代动力学研究证实,与市售缓释胶囊相比,3DOMG提高了口服生物利用度。这些发现证实,3DOMG可被视为一种有前途的口服药物递送系统载体。

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