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γ-环糊精金属有机框架作为载体递送雷公藤内酯醇治疗肝细胞癌。

γ-Cyclodextrin metal-organic framework as a carrier to deliver triptolide for the treatment of hepatocellular carcinoma.

机构信息

Department of Pharmacy, Shanghai 9Th People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 280 Mohe Road, Shanghai, 201999, China.

出版信息

Drug Deliv Transl Res. 2022 May;12(5):1096-1104. doi: 10.1007/s13346-021-00978-7. Epub 2021 Apr 15.

Abstract

Triptolide (TPL) has been employed to treat hepatocellular carcinoma (HCC). However, the poor water solubility of TPL restricts its applications. Therefore, we prepared TPL-loaded cyclodextrin-based metal-organic framework (TPL@CD-MOF) to improve the solubility and bioavailability of TPL, thus enhancing the anti-tumor effect on HCC. The BET surface and the pore size of TPL@CD-MOF were 10.4 m·g and 1.1 nm, respectively. The results of XRD indicated that TPL in TPL@CD-MOF was encapsuled. TPL@CD-MOF showed a slower release than free TPL in vitro. Moreover, the CD-MOF improved the bioavailability of TPL. TPL@CD-MOF showed slightly higher, but statistically significant, anti-tumor efficacy in vitro and in vivo compared to free TPL. In addition, TPL@CD-MOF exhibited a modest improvement of the anti-tumor effects, which may be associated to the enhanced in vivo absorption. Overall, these findings suggested the potential CD-MOF as oral drug delivery carriers for anti-tumor drugs. The process of TPL loading into CD-MOF and its enhanced oral bioavailability and anti-tumor activity.

摘要

雷公藤红素(TPL)已被用于治疗肝细胞癌(HCC)。然而,TPL 的水溶性差限制了其应用。因此,我们制备了载雷公藤红素的环糊精基金属有机骨架(TPL@CD-MOF),以提高 TPL 的溶解度和生物利用度,从而增强对 HCC 的抗肿瘤作用。TPL@CD-MOF 的 BET 表面积和孔径分别为 10.4 m·g 和 1.1 nm。XRD 结果表明 TPL 被包封在 TPL@CD-MOF 中。TPL@CD-MOF 在体外的释放速度比游离 TPL 慢。此外,CD-MOF 提高了 TPL 的生物利用度。与游离 TPL 相比,TPL@CD-MOF 在体外和体内显示出稍高但具有统计学意义的抗肿瘤疗效。此外,TPL@CD-MOF 显示出抗肿瘤作用的适度改善,这可能与体内吸收的增强有关。总的来说,这些发现表明 CD-MOF 有潜力作为抗肿瘤药物的口服药物递送载体。TPL 加载到 CD-MOF 中的过程及其增强的口服生物利用度和抗肿瘤活性。

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