Glycyrrhetinic acid-modified poly(ethylene glycol)-b-poly(gamma-benzyl l-glutamate) micelles for liver targeting therapy.
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.
Huang
Wei
W
Institute of Polymer Chemistry, Nankai University, Tianjin, People's Republic of China.
Wang
Wei
W
Wang
Ping
P
Tian
Qin
Q
Zhang
Chuangnian
C
Wang
Chunhong
C
Yuan
Zhi
Z
Liu
Min
M
Wan
Haiying
H
Tang
Hua
H
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
D000893:Anti-Inflammatory Agents; D000903:Antibiotics, Antineoplastic; D001672:Biocompatible Materials; D008823:Micelles; D011099:Polyglutamic Acid; D011092:Polyethylene Glycols; D004317:Doxorubicin; D006034:Glycyrrhetinic Acid