Li Juan, Yin Mingxing, Tian Maoxian, Fang Jianguo, Xu Hanlin
School of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China.
Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Pharmaceutics. 2024 Oct 7;16(10):1303. doi: 10.3390/pharmaceutics16101303.
Nonalcoholic fatty liver disease (NAFLD) poses a risk for numerous metabolic diseases. To date, the U.S. Food and Drug Administration has not yet approved any medications for the treatment of NAFLD, for which developing therapeutic drugs is urgent. Dihydromyricetin (DMY), the most abundant flavonoid in vine tea, has been shown to be hepatoprotective. Its application was limited by low bioavailability in vivo; In order to improve the bioavailability of DMY and achieve liver-targeted delivery, we designed a DMY-loaded stiff-soft hybrid biomimetic nano drug delivery system (DMY-hNE). The in vivo absorption, distribution, pharmacokinetic profiles, and anti-NAFLD efficacy of DMY-hNE were studied; DMY-hNE was composed of a stiff core and soft shell, which led to enhanced uptake by gastrointestinal epithelial cells and increased penetration of the mucus barrier, thus improving the in vivo absorption, plasma DMY concentration, and liver distribution versus free DMY. In an early NAFLD mouse model, DMY-hNE effectively ameliorated fatty lesions accompanied with reduced lipid levels and liver tissue inflammation; These findings suggested that DMY-hNE is a promising platform for liver drug delivery and treatment of hepatopathy.
非酒精性脂肪性肝病（NAFLD）会引发多种代谢性疾病。迄今为止，美国食品药品监督管理局尚未批准任何用于治疗NAFLD的药物，因此开发治疗药物迫在眉睫。二氢杨梅素（DMY）是藤茶中含量最丰富的黄酮类化合物，已被证明具有肝脏保护作用。其应用受到体内低生物利用度的限制；为了提高DMY的生物利用度并实现肝脏靶向递送，我们设计了一种载有DMY的硬-软混合仿生纳米药物递送系统（DMY-hNE）。研究了DMY-hNE的体内吸收、分布、药代动力学特征及抗NAFLD疗效；DMY-hNE由硬芯和软壳组成，导致胃肠道上皮细胞对其摄取增强，黏液屏障的穿透性增加，从而相对于游离DMY提高了体内吸收、血浆DMY浓度和肝脏分布。在早期NAFLD小鼠模型中，DMY-hNE有效改善了脂肪病变，同时降低了脂质水平和肝组织炎症；这些发现表明，DMY-hNE是一种有前景的肝脏药物递送和肝病治疗平台。
