Review
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 28, 2022; 28(36): 5280-5299
Published online Sep 28, 2022. doi: 10.3748/wjg.v28.i36.5280
Liver-specific drug delivery platforms: Applications for the treatment of alcohol-associated liver disease
Jeffrey Barr Warner, Steven Corrigan Guenthner, Josiah Everett Hardesty, Craig James McClain, Dennis Ray Warner, Irina Andreyevna Kirpich
Jeffrey Barr Warner, Steven Corrigan Guenthner, Josiah Everett Hardesty, Craig James McClain, Dennis Ray Warner, Irina Andreyevna Kirpich, Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY 40202, United States
Jeffrey Barr Warner, Irina Andreyevna Kirpich, Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, United States
Craig James McClain, Irina Andreyevna Kirpich, Alcohol Research Center, University of Louisville School of Medicine, Louisville, KY 40202, United States
Craig James McClain, Irina Andreyevna Kirpich, Hepatobiology and Toxicology Center, University of Louisville School of Medicine, Louisville, KY 40202, United States
Craig James McClain, Veterans Health Administration, Robley Rex Veterans Medical Center, Louisville, KY 40206, United States
Irina Andreyevna Kirpich, Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY 40202, United States
Author contributions: Warner JB and Kirpich IA designed and outlined the review; Warner JB wrote the contents of the review; Warner JB and Guenthner SC designed the figures; Guenthner SC, Hardesty JE, McClain CJ, Warner DR, and Kirpich IA edited the manuscript; all authors have read and approve the final manuscript.
Supported by National Institutes of Health, No. R01AA028905-01A1 (to Kirpich IA), No. 1F31AA028423-01A1 (to Warner JB), No. F32AA027950-01A1 (to Hardesty JE) and No. U01AA026934 (to McClain CJ); Jewish Heritage Fund for Excellence Research Enhancement Grant Program at the University of Louisville, as well as an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health, No. P20GM113226 (to McClain CJ); and National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health, No. P50AA024337 (to McClain CJ).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Irina Andreyevna Kirpich, MPH, PhD, Associate Professor, Department of Microbiology and Immunology, University of Louisville School of Medicine, 505 S. Hancock St., Louisville, KY 40202, United States. irina.kirpich@louisville.edu
Received: June 24, 2022
Peer-review started: June 24, 2022
First decision: August 6, 2022
Revised: August 16, 2022
Accepted: September 6, 2022
Article in press: September 6, 2022
Published online: September 28, 2022
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.

Keywords: Liver targeted delivery, Nanoparticles, Liposomes, Polymeric nanoparticles, Precision medicine, Alcohol associated liver disease

Core Tip: Alcohol-associated liver disease (ALD) is a common chronic liver disease and global healthcare burden. While a great deal of pre-clinical research attention is paid to ALD, many experimental therapeutics which are administered systemically suffer from poor pharmacokinetics or poor efficacy. Liver-targeted delivery may address these drawbacks while avoiding extra-hepatic side effects. This article reviews literature applying liver-targeted drug delivery platforms such as liposomes, exosomes, polymeric nanoparticles, viruses, and bioengineered bacteria to the treatment of ALD.