title: 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.affiliation: Institute of Polymer Chemistry, Nankai University, Tianjin, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Qin
authors.initials: Q
authors.lastname: Tian
authors.forename: Chuangnian
authors.initials: C
authors.lastname: Zhang
authors.forename: Chunhong
authors.initials: C
authors.lastname: Wang
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yuan
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.forename: Haiying
authors.initials: H
authors.lastname: Wan
authors.forename: Hua
authors.initials: H
authors.lastname: Tang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000378:metabolism; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000494:pharmacology; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology; D016503:Drug Delivery Systems; D005260:Female; D006034:Glycyrrhetinic Acid / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008422:Materials Testing; D008823:Micelles; D015394:Molecular Structure; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000378:metabolism; D011099:Polyglutamic Acid / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D000893:Anti-Inflammatory Agents; D000903:Antibiotics, Antineoplastic; D001672:Biocompatible Materials; D008823:Micelles; D011099:Polyglutamic Acid; D011092:Polyethylene Glycols; D004317:Doxorubicin; D006034:Glycyrrhetinic Acid