Liver-specific drug delivery platforms: Applications for the treatment of alcohol-associated liver disease

Abstract

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.

Enhancement of Liver Targetability through Statistical Optimization and Surface Modification of Biodegradable Nanocapsules Loaded with Lamivudine

“…Te opsonized nanoparticles can be readily engulfed by the reticuloendothelial system (RES) rich organs such as liver and spleen [58,59]. Tis mechanism of phagocytosis is even more prominent for the nanoparticles with a negative charge and with a size of above 200 nm [57]. Tese possible mechanisms could be responsible for the greater accumulation of the LMV from the PLGA nanoparticles developed in this work.…”

“…Te authors attributed this observation to the surface hydrophobicity of the nanoparticles owing to the presence of cholesterol. Few other similar reports regarding the passive liver targeting ability of nanoparticles are reviewed by Warner et al [57].…”

Emerging Roles of Spatial Transcriptomics in Liver Research

“…Spatial dissection of pathogenic cell types and cell–cell interactions with neighboring cells in the complicated liver architecture has the capability to substantially improve therapeutic efficacy by directing specific cell type. 130 Integration with other rapidly evolving technologies such as artificial intelligence-based pathology may contribute to development of novel biomarkers for disease progression and therapeutic response. 131 However, various barriers obstruct the translation of these discoveries into real-world clinical practice.…”