hepatocyteselective

Hepatocyteselective, more commonly written hepatocyte-selective, is a descriptive term in pharmacology and drug delivery referring to strategies, compounds, or approaches that preferentially affect or accumulate in hepatocytes, the main parenchymal cells of the liver, relative to other cell types. It encompasses actions that are localized to hepatocytes and approaches that aim to minimize systemic exposure and unintended effects elsewhere in the body.

Mechanisms and approaches include receptor-mediated uptake via the asialoglycoprotein receptor (ASGPR) on hepatocytes, often using GalNAc ligands to achieve selective internalization. Prodrugs designed to be activated primarily by hepatic enzymes, or vectors and genetic constructs with hepatocyte-specific expression control, also contribute to hepatocyte selectivity. Formulation and physicochemical properties can bias distribution toward the liver, such as nanoparticles or lipid-based systems that exhibit liver tropism.

Applications of hepatocyte selectivity span therapeutic delivery and diagnostic imaging. In therapeutics, hepatocyte-selective strategies enable delivery of nucleic acids (such as siRNA or antisense oligonucleotides), genes, or proteins to treat inherited liver diseases, metabolic disorders, and some viral infections. In imaging, hepatocyte-targeted agents can improve liver-specific contrast or signal. These approaches aim to enhance efficacy within the liver while reducing exposure and toxicity in nonhepatic tissues.

Challenges include variability in receptor expression among individuals and species, potential off-target uptake by nonhepatic tissues, immune responses, and safety concerns with repeated dosing or long-term therapy. Hepatocyte selectivity is related to, but distinct from, liver specificity, which describes activity confined to liver tissue regardless of distribution.