Mechanism of liver injury and design of drug delivery system for the liver.

目前尚无临床有效的治疗方法治疗暴发性肝炎。肝炎的主要机制是由于肝脏内肝细胞的细胞死亡。事实上，多种肝炎可以通过使用细胞凋亡抑制剂来抑制。然而，这些抑制剂对肝细胞不具有特异性，因此在体内表现出各种副作用。因此，我们开发了肝细胞特异性纳米颗粒，由表面含有半乳糖聚合物（PVLA）的聚乳酸组成。包裹caspase（凋亡执行剂）抑制剂的纳米颗粒与肝细胞特异性相互作用，释放时间较长，即比对照组（1小时）超过24小时。结果，这种类型的纳米颗粒在体外有效地抑制fas介导和ifn - γ介导的肝细胞死亡。此外，这些纳米颗粒还能在体内抑制t细胞介导的小鼠肝炎，这被认为是人类病毒性肝炎的典型模型。在体内，纳米颗粒特异性地积聚在肝脏的肝细胞中。这些颗粒没有在其他器官中积聚。这些颗粒具有器官特异性，有效时间延长。

Any clinically effective therapy does not exist for fulminant hepatitis. The main mechanism of hepatitis is due to the cell death of hepatocytes in the liver. In fact, various hepatitis can be suppressed by the administration of apoptosis inhibitors. However, these inhibitors do not have the specificity for hepatocytes, thus, showed various side effects in vivo. Therefore, we developed hepatocyte-specific nanoparticles composed of poly-lactic acid bearing galactose polymer (PVLA) on the surface. The nanoparticles encapsulated caspase (excutioner of apoptosis) inhibitor specifically interacted with hepatocytes and release the contents in the cytosol for longer period, i.e., more than 24 h compared to the control (1 h). As a result, this type of nanoparticles efficiently suppressed the Fas-mediated and IFN-gamma-mediated hepatocyte cell death in vitro. In addition, these nanoparticles also inhibited the T-cell mediated mouse hepatitis, which is thought to be a typical model of human virus hepatitis, in vivo. In vivo, the nanoparticles specifically accumulated in the hepatocytes of the liver. These particles did not accumulate in other organs. These particles showed the organ specificity and elongated effective period.