Efficient Hepatic Delivery of Drugs: Novel Strategies and Their Significance

Abstract

Liver is a vital organ responsible for plethora of functions including detoxification, protein synthesis, and the production of biochemicals necessary for the sustenance of life. Therefore, patients with chronic liver diseases such as viral hepatitis, liver cirrhosis, and hepatocellular carcinoma need immediate attention to sustain life and as a result are often exposed to the prolonged treatment with drugs/herbal medications. Lack of site-specific delivery of these medications to the hepatocytes/nonparenchymal cells and adverse effects associated with their off-target interactions limit their continuous use. This calls for the development and fabrication of targeted delivery systems which can deliver the drug payload at the desired site of action for defined period of time. The primary aim of drug targeting is to manipulate the whole body distribution of drugs, that is, to prevent distribution to non-target cells and concomitantly increase the drug concentration at the targeted site. Carrier molecules are designed for their selective cellular uptake, taking advantage of specific receptors or binding sites present on the surface membrane of the target cell. In this review, various aspects of liver targeting of drug molecules and herbal medications have been discussed which elucidate the importance of delivering the drugs/herbal medications at their desired site of action.

Lactoferrin-modified PEGylated liposomes loaded with doxorubicin for targeting delivery to hepatocellular carcinoma

“…Repeated attempts have been made to deliver drugs specifically to HCC via ASGPR because of their high affinity and rapid internalization in hepatic tumor cells. 11,13,14 Recent researches demonstrated that Lf might be a potential HCC ligand because of its specific binding with ASGPR. 14,[19][20][21] And Lf exhibits its active targeting ability for HCC cells by the ASGPR endocytosis process.…”

“…11,13,14 Recent researches demonstrated that Lf might be a potential HCC ligand because of its specific binding with ASGPR. 14,[19][20][21] And Lf exhibits its active targeting ability for HCC cells by the ASGPR endocytosis process. 14,[19][20][21] Our previous work also confirmed the HCC-targeting effect of PLS modified with Lf.…”

“…14,[19][20][21] And Lf exhibits its active targeting ability for HCC cells by the ASGPR endocytosis process. 14,[19][20][21] Our previous work also confirmed the HCC-targeting effect of PLS modified with Lf. 21 Thus, Lf was applied to be the ASGPR-targeting ligand in this work.…”

“…11,13 Recently, lactoferrin (Lf), a mammalian cationic iron-binding glycoprotein belonging to the Tf family, has been demonstrated to bind ASGPR with high affinity in a galactoseindependent manner. [14][15][16][17] It might be suggested that Lf is a good ligand for ASGPR binding. With its specific binding, Lf has been applied to gene delivery successfully, and its ability to target hepatic tumor cells also has been confirmed.…”

Liver X receptor α (LXRα/NR1H3) regulates differentiation of hepatocyte-like cells via reciprocal regulation of HNF4α

“…The addition of NR1H3 agonists into differentiation cocktails might also be beneficial for the generation of functional hepatocyte-like cells from other stem cell resources and for further studies of hepatocyte transplantation in end-stage liver disease. Finally, it is also possible to accelerate liver regeneration in vivo by liver-specific target delivery of NR1H3 agonists, such as to package agonists into liver-specific vehicles [54,55].…”