Liver cell-targeted delivery of therapeutic molecules

Abstract

The liver is the largest internal organ in mammals and is involved in metabolism, detoxification, synthesis of proteins and lipids, secretion of cytokines and growth factors and immune/inflammatory responses. Hepatitis, alcoholic or non-alcoholic liver disease, hepatocellular carcinoma, hepatic veno-occlusive disease, and liver fibrosis and cirrhosis are the most common liver diseases. Safe and efficient delivery of therapeutic molecules (drugs, genes or proteins) into the liver is very important to increase the clinical efficacy of these molecules and to reduce their side effects in other organs. Several liver cell-targeted delivery systems have been developed and tested in vivo or ex vivo/in vitro. In this review, we discuss the literature concerning liver cell-targeted delivery systems, with a particular emphasis on the results of in vivo studies.

Nanomaterial Manipulation of Immune Microenvironment in the Diseased Liver

“…Receptor‐Mediated Targeting : Liver cells express a variety of different membrane receptors, mainly including carbohydrate receptors (e.g., asialoglycoprotein receptor, ASGP‐R, mannose receptor) and scavenger receptors, facilitating the development of liver‐targeted delivery system as summarized in ref. ]. However, NPs equipped with high‐affinity ligands toward these receptors are not guaranteed to accumulate in the specific hepatic cells due to the overlapped receptor expression pattern, especially for carbohydrate receptors.…”

“…For instance, both KCs and LSECs express mannose receptors and scavenger receptors . Although the mannose receptors on KCs demonstrate greater affinity for mannose, the endocytic efficiency for mannose conjugated NPs in two kinds of cells might be similar due to the twofold greater number of LSECs and higher expression of the receptor in LSECs, which suggests the identification of off‐target effects is necessary when targeting the specific liver cell via the shared receptors. Similarly, ASGP‐R, which was regarded as a hepatocyte‐specific receptor previously, was recently found to be also expressed on KCs and LSECs for platelet phagocytosis .…”

Comparative pharmacokinetics of the main compounds of Shanzhuyu extract after oral administration in normal and chronic kidney disease rats

“…Drugs are used to treat diseases and only patients are the ultimate consumers. The pathological status and severity of disease seriously affects the drug absorption, which is directly related to drug efficacy and severity of side effects (Kang et al, 2014;Reid and Carlson, 2014;Schuetz et al, 2014).…”

Liver Cancer: Current and Future Trends Using Biomaterials

“…Nano-to-micro range biomaterials are generally used for treatment, whereas, macroscale materials, in the form of tissue engineering scaffolds, are used for study this tumor. There are many review articles on nanotechnology/nanomedicine for liver cancer therapy, such as nanoparticles (NPs) and liposomes [1][2][3][4][5][6][7][8], liver cancer diagnosis and therapy [9], and biomaterials used for targeted systems [10]. However, there are no comprehensive reviews of biomaterial-based therapy that includes an overview of materials in the nano-to-macro domain, which also includes microparticles and scaffolds, with a discussion of both systemic and local delivery applications.…”