水飞蓟宾-壳聚糖纳米粒的绿色合成：一种新型纳米制剂，具有增强的抗肝纤维化作用。
Green Synthesis of Silymarin-Chitosan Nanoparticles as a New Nano Formulation with Enhanced Anti-Fibrotic Effects against Liver Fibrosis.
机构信息
Department of Chemistry, Faculty of Science, Menoufia University, Shebin El Koom 13829, Egypt.
Department of Chemistry, Faculty of Education, Thamar University, Thamar 63022, Yemen.
出版信息
Int J Mol Sci. 2022 May 12;23(10):5420. doi: 10.3390/ijms23105420.
BACKGROUND
Silymarin (SIL) has long been utilized to treat a variety of liver illnesses, but due to its poor water solubility and low membrane permeability, it has a low oral bioavailability, limiting its therapeutic potential.
AIM
Design and evaluate hepatic-targeted delivery of safe biocompatible formulated SIL-loaded chitosan nanoparticles (SCNPs) to enhance SIL's anti-fibrotic effectiveness in rats with CCl-induced liver fibrosis.
METHODS
The SCNPs and chitosan nanoparticles (CNPs) were prepared by ionotropic gelation technique and are characterized by physicochemical parameters such as particle size, morphology, zeta potential, and in vitro release studies. The therapeutic efficacy of successfully formulated SCNPs and CNPs were subjected to in vivo evaluation studies. Rats were daily administered SIL, SCNPs, and CNPs orally for 30 days.
RESULTS
The in vivo study revealed that the synthesized SCNPs demonstrated a significant antifibrotic therapeutic action against CCl-induced hepatic injury in rats when compared to treated groups of SIL and CNPs. SCNP-treated rats had a healthy body weight, with normal values for liver weight and liver index, as well as significant improvements in liver functions, inflammatory indicators, antioxidant pathway activation, and lipid peroxidation reduction. The antifibrotic activities of SCNPs were mediated by suppressing the expression of the main fibrosis mediators TGFβR1, COL3A1, and TGFβR2 by boosting the hepatic expression of protective miRNAs; miR-22, miR-29c, and miR-219a, respectively. The anti-fibrotic effects of SCNPs were supported by histopathology and immunohistochemistry (IHC) study.
CONCLUSIONS
According to the above results, SCNPs might be the best suitable carrier to target liver cells in the treatment of liver fibrosis.
背景
水飞蓟素（SIL）长期以来一直被用于治疗各种肝脏疾病，但由于其水溶性差和细胞膜通透性低，口服生物利用度低，限制了其治疗潜力。
目的
设计并评价安全生物相容的载有水飞蓟素的壳聚糖纳米粒（SCNPs）的肝靶向递送来增强 SIL 在 CCl 诱导的肝纤维化大鼠中的抗纤维化效果。
方法
通过离子凝胶技术制备 SCNPs 和壳聚糖纳米粒（CNPs），并通过粒径、形态、Zeta 电位和体外释放研究等理化参数进行表征。成功制备的 SCNPs 和 CNPs 的治疗效果进行了体内评价研究。大鼠每天口服给予 SIL、SCNPs 和 CNPs30 天。
结果
体内研究表明，与 SIL 和 CNPs 治疗组相比，合成的 SCNPs 对 CCl 诱导的肝损伤大鼠具有显著的抗纤维化治疗作用。SCNP 治疗组大鼠体重健康，肝重和肝指数正常，肝功能、炎症指标、抗氧化途径激活和脂质过氧化降低均有显著改善。SCNPs 的抗纤维化作用是通过抑制主要纤维化介质 TGFβR1、COL3A1 和 TGFβR2 的表达，同时通过增强保护性 miRNA 的肝表达来介导的；分别为 miR-22、miR-29c 和 miR-219a。SCNPs 的抗纤维化作用得到了组织病理学和免疫组织化学（IHC）研究的支持。
结论
根据上述结果，SCNPs 可能是治疗肝纤维化的最佳合适载体，以靶向肝细胞。
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