Self-assembly and liver targeting of sulfated chitosan nanoparticles functionalized with glycyrrhetinic acid

A drug carrier based on glycyrrhetinic acid-modified sulfated chitosan (GA-SCTS) was synthesized. The glycyrrhetinic acid (GA) acted as both a hydrophobic group and a liver-targeting ligand. The GA-SCTS micelles displayed rapid and significant ability to target the liver in vivo. The IC 50 for doxorubicin (DOX)-loaded GA-SCTS micelles (DOX/SA-SCTS micelles) against HepG2 cells was 54.7 ng/mL, which was extremely lower than the amount of no-GA-modified DOX-loaded micelles. In addition, DOX/SA-SCTS micelles could target specifically the liver cancer cells. They had higher affinity for the liver cancer cells (HepG2 cells) than for the normal liver cells (Chang liver cells). There was nearly 2.18-fold improvement in uptake of the DOX/SA-SCTS micelles by HepG2 cells than that by Chang liver cells. These results indicate that GA-SCTS is not only an excellent carrier for drugs, but also a potential vehicle for liver-cancer targeting. In this basic science study, sulfated chitosan nanoparticles were functionalized with glycyrrhetinic acid and studied in cell cultures, demonstrating efficient self-assembly and targeting of liver pathology. In vivo demonstration for the same is also provided, paving the way to future studies establishing long-term effects, toxicity and potential clinical applicability. Glycyrrhetinic acid (GA)-modified carriers are more efficient for liver- or hepatocyte-targeted delivery; however, less information is available about their biodistribution, and there is no information that GA-modified drug delivery system has the ability to target specifically the liver cancer cells. Therefore, GA-modified sulfated chitosan (GA-SCTS) polymeric micelles were designed and prepared in this work. The biodistribution and in vitro cellular uptake assays were investigated. GA-SCTS micelles had several advantages, such as the low CAC (critical aggregation concentration) value, high encapsulation efficacy, and high loading content for doxorubicin (DOX). In addition, they displayed rapid and significant ability to target the liver in vivo. It is important to note that GA-SCTS micelles had higher affinity for HepG2 cells (liver cancer cells) than for Chang liver cells (liver normal cells).