Glycyrrhetinic acid-modified poly(ethylene glycol)-b-poly(gamma-benzyl l-glutamate) micelles for liver targeting therapy.

Abstract

Liver targeted micelles were successfully constructed via self-assembly of glycyrrhetinic acid (GA)-modified poly(ethylene glycol)-b-poly(gamma-benzyl l-glutamate) (GA-PEG-PBLG) block co-polymers, which were fabricated via ring opening polymerization of gamma-benzyl l-glutamate N-carboxyanhydride monomer initiated by GA-modified PEG. The in vivo biodistribution and the in vitro cellular uptake of these micelles were investigated. The results showed that the relative uptake of doxorubicin (DOX)-loaded micelles (DOX/GA-PEG-PBLG) in liver was much higher than in other tissues, and the resulting DOX concentration in liver was about 2.2-fold higher than that from the micelles without modification by GA. Moreover, the cellular uptake study demonstrated that the introduction of GA to the micelles could significantly increase the affinity for human hepatic carcinoma 7703 cells, which induced a 3.7-fold higher endocytosis than unmodified ones. The cytotoxicity of DOX/GA-PEG-PBLG micelles (IC(50) 47 ngml(-1)) was much higher than that of free DOX (IC(50) 90 ngml(-1)). These results indicate that GA-modified micelles have great potential in liver targeting therapy.

• Authors: Wei Huang, Wei Wang, Ping Wang, Qin Tian, Chuangnian Zhang, Chunhong Wang, Zhi Yuan, Min Liu, Haiying Wan, Hua Tang
• Journal: Acta biomaterialia (Acta Biomater) Vol. 6 Issue 10 Pg. 3927-35 (Oct 2010) ISSN: 1878-7568 [Electronic] England
• PMID: 20438873 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Antibiotics, Antineoplastic
• Biocompatible Materials
• Micelles
• Polyglutamic Acid
• Polyethylene Glycols
• Doxorubicin
• Glycyrrhetinic Acid

Topics

• Animals
• Anti-Inflammatory Agents (chemistry, metabolism)
• Antibiotics, Antineoplastic (chemistry, pharmacology)
• Biocompatible Materials (chemistry, metabolism)
• Cell Line
• Doxorubicin (chemistry, pharmacology)
• Drug Delivery Systems
• Female
• Glycyrrhetinic Acid (chemistry, metabolism)
• Humans
• Liver (drug effects, metabolism)
• Materials Testing
• Micelles
• Molecular Structure
• Polyethylene Glycols (chemistry, metabolism)
• Polyglutamic Acid (chemistry, metabolism)
• Rats
• Rats, Wistar
• Tissue Distribution