Liver-targeted drug delivery systems of traditional Chinese medicine: a novel strategy for the treatment of fatty liver disease

Fatty liver disease (FLD) is the most prevalent chronic liver disease worldwide, and its prevalence continues to rise steadily each year. FLD is not only a major predisposing factor for liver fibrosis, cirrhosis, and hepatocellular carcinoma, but is also closely associated with various extrahepatic diseases such as cardiovascular disease and chronic kidney disease, imposing a heavy burden on global healthcare systems. Currently, treatment options for FLD are limited. In contrast, traditional Chinese medicine (TCM) has a long history in treating FLD and has shown certain efficacy. However, most TCM compounds face limitations, including poor water solubility, low in vivo bioavailability, and insufficient liver-targeting ability, which hinder their effective accumulation at hepatic lesion sites. This article reviews the TCM monomer compounds used in the treatment of FLD, as well as the characteristics and recent advances in passive liver-targeting drug delivery systems, active liver-targeting systems, and smart drug-targeting systems. It also elucidates the challenges and development prospects of liver-targeting strategies in TCM therapeutic applications, aiming to promote the clinical translation and application of novel liver-targeted delivery drugs derived from TCM for the treatment of FLD.