肝靶向共同递送基于白蛋白纳米颗粒的恩替卡韦和甘草次酸

StephenW

Mol Pharm. 2018 Aug 15. doi: 10.1021/acs.molpharmaceut.8b00408. [Epub ahead of print]
Liver targeted co-delivery of entecavir and glycyrrhetinic acid based on albumin nanoparticle to enhance the accumulation of entecavir.
He S, Lin Q, Qu M, Wang L, Deng L, Xiao L, Zhang Z, Zhang L.
Abstract

Hepatitis B, one of the most common contagious viral hepatitis with high infection rate, is challenging to treat. Although the treatment for hepatitis B has been improved over the years, many therapeutic drugs still have either severe adverse effects or insufficient effectiveness via systemic administration. In this study, we confirmed that glycyrrhetinic acid can enhance the accumulation of entecavir in HepaRG cell and liver. Then we constructed a novel albumin nanoparticle co-loading entecavir and glycyrrhetinic acid (ETV-GA-AN) to improve liver accumulation of entecavir and investigated its ability to deliver both drugs to liver. In vitro cellular uptake study and in vivo tissue distribution experiment show that these negatively charged ETV-GA-AN (112 ± 2 nm in diameter) can increase the accumulation of entecavir in hepatic HepaRG cells and improve entecavir distribution in liver. We also revealed the mechanism that glycyrrhetinic acid enhances intracellular accumulation of entecavir by inhibiting the activity of specific efflux transporters. Our delivery system is the first liver-targeted albumin nanoparticle that utilizes the site-specific co-delivery strategy to delivery entecavir and glycyrrhetinic acid. As it combines high efficiency and low toxicity, it possess great potential for treating hepatitis B.

PMID:
    30110554
DOI:
    10.1021/acs.molpharmaceut.8b00408

StephenW

Mol Pharm。 2018年8月15日doi：10.1021 / acs.molpharmaceut.8b00408。 [提前打印]
肝靶向共同递送基于白蛋白纳米颗粒的恩替卡韦和甘草次酸，以增强恩替卡韦的积累。
何思，林琦，曲敏，王莉，邓璐，肖莉，张,,张莉
抽象

治疗乙肝是最常见的感染率较高的传染性病毒性肝炎之一。尽管多年来乙型肝炎的治疗已有所改善，但许多治疗药物仍然具有严重的副作用或通过全身给药不足。在这项研究中，我们证实甘草次酸可以增强恩替卡韦在HepaRG细胞和肝脏中的积累。然后，我们构建了一种新型白蛋白纳米粒子共加载恩替卡韦和甘草次酸（ETV-GA-AN），以改善恩替卡韦的肝脏积聚，并研究其向肝脏输送两种药物的能力。体外细胞摄取研究和体内组织分布实验表明，这些带负电荷的ETV-GA-AN（直径112±2nm）可以增加恩替卡韦在肝脏HepaRG细胞中的积累，并改善肝脏中恩替卡韦的分布。我们还揭示了甘草次酸通过抑制特定外排转运蛋白的活性来增强恩替卡韦的细胞内积累的机制。我们的输送系统是第一个肝靶向白蛋白纳米颗粒，利用特定位点的共同递送策略来递送恩替卡韦和甘草次酸。由于它结合了高效率和低毒性，它具有治疗乙型肝炎的巨大潜力。

结论：
    30110554
DOI：
    10.1021 / acs.molpharmaceut.8b00408

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