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

Add time:09/10/2019    Source:sciencedirect.com

Liver targeted micelles were successfully constructed via self-assembly of glycyrrhetinic acid (GA)-modified poly(ethylene glycol)–b-poly(γ-benzyl l-glutamate) (GA–PEG–PBLG) block co-polymers, which were fabricated via ring opening polymerization of γ-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 (IC50 47 ng ml−1) was much higher than that of free DOX (IC50 90 ng ml−1). These results indicate that GA-modified micelles have great potential in liver targeting therapy.

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