Abstract

Liver fibrosis is a key pathological process shared by the progression of various chronic liver diseases. Treatment of liver fibrosis can effectively block the occurrence and development of hepatic cirrhosis or even carcinoma. Currently, there is no effective drug delivery vehicle for curing liver fibrosis. In this study, we designed matrine (MT)-loaded mannose 6-phosphate (M6P) modified human serum albumin (HSA) conjugated solid lipid nanoparticles (SLN), named M6P-HSA-MT-SLN for treatment of hepatic fibrosis. We demonstrated that M6P-HSA-MT-SLN exhibited controlled and sustained release properties and good stability over 7 days. The drug release experiments showed that M6P-HSA-MT-SLN exhibited slow and controlled drug release characteristics. In addition, M6P-HSA-MT-SLN showed a significant targeted ability to fibrotic liver. Importantly, in vivo studies indicated that M6P-HSA-MT-SLN could significantly improve histopathological morphology and inhibit the fibrotic phenotype. In addition, in vivo experiments demonstrate that M6P-HSA-MT-SLN could reduce the expression of fibrosis markers and alleviate the damage of liver structure. Hence, the M6P-HSA-MT-SLN provide a promising strategy to deliver therapeutic agents to fibrotic liver to prevent liver fibrosis.

摘要

肝纤维化是多种慢性肝病进展所共有的关键病理过程。治疗肝纤维化可以有效阻断肝硬化甚至癌的发生和发展。目前，尚无有效的治疗肝纤维化的药物递送载体。在本研究中，我们设计了负载苦参碱（MT）的6-磷酸甘露糖（M6P）修饰的人血清白蛋白（HSA）缀合的固体脂质纳米粒（SLN），命名为M6P-HSA-MT-SLN，用于治疗肝纤维化。我们证明 M6P-HSA-MT-SLN 在 7 天内表现出控释和缓释特性以及良好的稳定性。药物释放实验表明M6P-HSA-MT-SLN表现出缓慢、受控的药物释放特性。此外，M6P-HSA-MT-SLN对纤维化肝脏表现出显着的靶向能力。重要的，体内研究表明M6P-HSA-MT-SLN可以显着改善组织病理学形态并抑制纤维化表型。此外，体内实验表明M6P-HSA-MT-SLN可以减少纤维化标志物的表达，减轻肝脏结构的损伤。因此，M6P-HSA-MT-SLN 提供了一种向纤维化肝脏输送治疗药物以预防肝纤维化的有前途的策略。