School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
J Nanobiotechnology. 2018 Sep 4;16(1):64. doi: 10.1186/s12951-018-0391-9.
Non-alcoholic fatty liver disease (NAFLD) is a chronic disease that causes excessive hepatic lipid accumulation. Reducing hepatic lipid deposition is a key issue in treatment and inhibition of NAFLD evolution. Silymarin is a potent hepatoprotective agent; however, it has low oral bioavailability due to its poor aqueous solubility and low membrane permeability. Unfortunately, few studies have addressed the development of convenient oral nanocarriers that can efficiently deliver silymarin to the liver and enhance its lipid-lowering effect. We designed silymarin-loaded lipid polymer hybrid nanoparticles containing chitosan (CS-LPNs) to improve silymarin bioavailability and evaluated their lipid-lowering effect in adiponutrin/patatin-like phospholipase-3 I148M transgenic mice, an NAFLD model.
Compared to chitosan-free nanoparticles, CS-LPNs showed 1.92-fold higher uptake by fatty liver cells. Additionally, CS-LPNs significantly reduced TG levels in fatty liver cells in an in vitro lipid deposition assay, suggesting their potential lipid-lowering effects. The oral bioavailability of silymarin from CS-LPNs was 14.38-fold higher than that from suspensions in rats. Moreover, compared with chitosan-free nanoparticles, CS-LPNs effectively reduced blood lipid levels (TG), improved liver function (AST and ALT), and reduced lipid accumulation in the livers of mice in vivo. Reduced macrovesicular steatosis in pathological tissue after CS-LPN treatment indicated their protective effect against liver steatosis in NAFLD.
CS-LPNs enhanced oral delivery of silymarin and exhibited a desirable lipid-lowering effect in a mouse model. These findings suggest that CS-LPNs may be a promising oral nanocarrier for NAFLD therapeutics.
非酒精性脂肪性肝病（NAFLD）是一种引起肝内脂质过度蓄积的慢性疾病。减少肝内脂质沉积是治疗和抑制 NAFLD 进展的关键。水飞蓟素是一种有效的肝保护剂；然而，由于其较差的水溶性和低膜通透性，其口服生物利用度较低。遗憾的是，很少有研究涉及开发方便的口服纳米载体，以有效地将水飞蓟素递送到肝脏并增强其降脂作用。我们设计了载有水飞蓟素的含壳聚糖的脂质聚合物杂化纳米粒（CS-LPNs），以提高水飞蓟素的生物利用度，并在脂肪转铁蛋白/类 patatin 磷脂酶 3 I148M 转基因小鼠（NAFLD 模型）中评估其降脂作用。
与不含壳聚糖的纳米粒相比，CS-LPNs 被脂肪肝细胞摄取的能力提高了 1.92 倍。此外，CS-LPNs 在体外脂质沉积试验中显著降低了脂肪肝细胞中的 TG 水平，表明其具有潜在的降脂作用。CS-LPNs 使水飞蓟素在大鼠体内的口服生物利用度提高了 14.38 倍。此外，与不含壳聚糖的纳米粒相比，CS-LPNs 有效地降低了血脂水平（TG），改善了肝功能（AST 和 ALT），并减少了小鼠体内肝脏的脂质蓄积。CS-LPN 治疗后病理组织中宏观微泡性脂肪变性减少表明其对 NAFLD 肝脂肪变性具有保护作用。
CS-LPNs 增强了水飞蓟素的口服递送，并在小鼠模型中表现出理想的降脂作用。这些发现表明 CS-LPNs 可能是治疗 NAFLD 的一种有前途的口服纳米载体。
