Liver-specific drug delivery platforms: Applications for the treatment of alcohol-associated liver disease.
Liver-specific drug delivery platforms: Applications for the treatment of alcohol-associated liver disease.
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DOI：
10.3748/wjg.v28.i36.5280
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发表时间：
2022-09-28
影响因子：
4.3
通讯作者：
Kirpich IA
中科院分区：
文献类型：
--
作者：
Warner JB;Guenthner SC;Hardesty JE;McClain CJ;Warner DR;Kirpich IA
酒精相关性肝病(ALD)是一种常见的慢性肝病，是全球肝病相关死亡的主要原因。尽管它的先效价，但几乎没有有效的药理选择来治疗这种疾病的严重阶段。虽然ALD的药物开发受到了很大的临床前研究的关注，但这些实验疗法中的许多都有局限性，如较差的药代动力学、较差的疗效或由于全身用药而产生的非靶点副作用。解决这些限制的一种方法是通过肝脏靶向给药，这可以通过不同的平台实现，包括脂质体、聚合纳米粒、外切体、细菌和腺相关病毒等。这些平台允许药物被动或主动地针对肝脏，从而减少全身循环，增加肝脏的有效剂量。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，但很少有人研究它们在ALD中的疗效。本文综述了这些肝靶向给药平台的基本情况，包括它们的优点和局限性，并总结了它们在啮齿动物模型中应用于ALD治疗的研究进展。我们还讨论了该领域的知识差距，如果解决了这些差距，可能有助于提高新疗法的有效性，并更好地将其转化为人类。
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.
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