Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY 40202, United States.
Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, United States.
World J Gastroenterol. 2022 Sep 28;28(36):5280-5299. doi: 10.3748/wjg.v28.i36.5280.
Alcohol-associated liver disease (ALD) is a common chronic liver disease and major contributor to liver disease-related deaths worldwide. Despite its pre-valence, there are few effective pharmacological options for the severe stages of this disease. While much pre-clinical research attention is paid to drug development in ALD, many of these experimental therapeutics have limitations such as poor pharmacokinetics, poor efficacy, or off-target side effects due to systemic administration. One means of addressing these limitations is through liver-targeted drug delivery, which can be accomplished with different platforms including liposomes, polymeric nanoparticles, exosomes, bacteria, and adeno-associated viruses, among others. These platforms allow drugs to target the liver passively or actively, thereby reducing systemic circulation and increasing the 'effective dose' in the liver. While many studies, some clinical, have applied targeted delivery systems to other liver diseases such as viral hepatitis or hepatocellular carcinoma, only few have investigated their efficacy in ALD. This review provides basic information on these liver-targeting drug delivery platforms, including their benefits and limitations, and summarizes the current research efforts to apply them to the treatment of ALD in rodent models. We also discuss gaps in knowledge in the field, which when addressed, may help to increase the efficacy of novel therapies and better translate them to humans.
酒精性肝病(ALD)是一种常见的慢性肝病,也是全球与肝病相关死亡的主要原因。尽管该病的发病率很高,但针对该病严重阶段的有效药物治疗选择却很少。尽管许多临床前研究都关注 ALD 的药物开发,但由于全身给药,许多这些实验性治疗方法存在局限性,如药代动力学不佳、疗效不佳或存在脱靶副作用。解决这些局限性的一种方法是通过肝靶向药物传递,这可以通过不同的平台来实现,包括脂质体、聚合物纳米颗粒、外泌体、细菌和腺相关病毒等。这些平台允许药物被动或主动靶向肝脏,从而减少系统循环并增加肝脏中的“有效剂量”。虽然许多研究(包括一些临床研究)已经将靶向递送系统应用于其他肝病,如病毒性肝炎或肝细胞癌,但只有少数研究调查了它们在 ALD 中的疗效。本文综述了这些肝靶向药物传递平台的基本信息,包括它们的优点和局限性,并总结了目前将它们应用于啮齿动物模型中 ALD 治疗的研究进展。我们还讨论了该领域的知识差距,这些差距的解决可能有助于提高新型疗法的疗效,并更好地将其转化为人类。
World J Gastroenterol. 2022-9-28
Rev Esp Enferm Dig. 2020-11
Adv Drug Deliv Rev. 2020
Addiction. 2021-5
Eur J Pharm Biopharm. 2015-6
Nihon Arukoru Yakubutsu Igakkai Zasshi. 2016-8
Int J Mol Sci. 2019-6-2
Antioxidants (Basel). 2025-7-24
Int J Nanomedicine. 2025-5-24
Drug Deliv Transl Res. 2025-6
Nat Commun. 2021-5-20
Mayo Clin Proc. 2021-4
World J Hepatol. 2020-7-27
Am J Physiol Gastrointest Liver Physiol. 2020-1-13