Dept. of Pharmacokinetics, Toxicology and Targeting, University of Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands.
J Control Release. 2012 Jul 20;161(2):188-97. doi: 10.1016/j.jconrel.2012.02.011. Epub 2012 Feb 17.
Many serious liver diseases affecting millions of people world-wide cannot be treated despite many efforts which warrants a search for new therapeutic strategies. Potent drugs may not be effective enough in vivo or exhibit adverse effects and enhanced delivery into the target cells may improve this significantly. We aim to summarize the available options for drug delivery to the different intrahepatic cell-types. The most relevant target cells are identified for each liver disease and the strategies for drug delivery to these cells are subsequently reviewed. The review describes the use of proteins, viruses, polymers and liposomes for therapeutic purposes in various liver diseases. It is shown that to date, all resident intrahepatic cells can be reached with several different drug carriers. Much progress has been made in recent years to deliver small drug molecules, proteins and nucleic acids specifically to the key pathogenic cells in vivo. The knowledge of drug targeting gained in the past decades, combined with a proper preclinical evaluation, may bring new therapeutics to the clinic in the near future.
尽管已经付出了许多努力，但仍有许多影响全球数百万人的严重肝脏疾病无法得到治疗，这就需要寻找新的治疗策略。尽管有强效药物，但它们在体内可能效果不够显著，或者表现出不良反应，而增强向靶细胞的递送可能会显著改善这种情况。我们旨在总结向不同肝内细胞类型递药的现有选择。为每种肝脏疾病确定了最相关的靶细胞，并随后回顾了向这些细胞递药的策略。该综述描述了蛋白质、病毒、聚合物和脂质体在各种肝脏疾病中的治疗用途。结果表明，迄今为止，已经可以使用几种不同的药物载体来接近所有驻留的肝内细胞。近年来，在将小分子药物、蛋白质和核酸特异性递送至体内关键致病细胞方面已经取得了很大进展。过去几十年中在药物靶向方面取得的知识，结合适当的临床前评估，可能会在不久的将来为临床带来新的治疗方法。
