Poelstra Klaas, Beljaars Leonie, Melgert Barbro N
Dept. of Pharmacokinetics, Toxicology & Targeting, University of Groningen, The Netherlands.
Drug Discov Today. 2013 Dec;18(23-24):1237-42. doi: 10.1016/j.drudis.2013.05.013. Epub 2013 May 31.
Liver fibrosis is a complex disease affecting millions of people world-wide. It involves the activation of several cell types whose activities are tightly controlled by endogenous mediators. No pharmacotherapy is available for this disease, despite the fact that many experimental drugs are very effective in vitro and the liver is easily accessible for most drugs. Our review provides arguments showing that cell-selectivity is essential for most antifibrotics. Several cell-specific drug carriers targeting the key pathogenic liver cells are discussed with special focus on hepatic stellate cells and fibroblast-like cells. Since endogenous mediators represent a powerful set of tools to modify the pathogenic process, this review focuses on these mediators as therapeutics and the problems and pitfalls associated with the use of such biologicals.
肝纤维化是一种影响全球数百万人的复杂疾病。它涉及多种细胞类型的激活，这些细胞的活动受到内源性介质的严格控制。尽管许多实验性药物在体外非常有效，而且大多数药物都很容易进入肝脏，但目前尚无针对这种疾病的药物疗法。我们的综述提供了证据表明，细胞选择性对大多数抗纤维化药物至关重要。本文讨论了几种靶向关键致病性肝细胞的细胞特异性药物载体，特别关注肝星状细胞和成纤维细胞样细胞。由于内源性介质是改变致病过程的有力工具集，因此本综述重点关注这些介质作为治疗方法以及使用此类生物制剂相关的问题和陷阱。
