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THAVASYAPPANTHAMBI,Gurusamy Saravanakumar,추준욱,허로운,고혜원,VEERASIKKUGOPAL DEEPAGAN,김종호,박재형 한국고분자학회 2013 Macromolecular Research Vol.21 No.1
An amphiphilic diblock copolymer bearing the reduction-sensitive linker, composed of poly(ethylene glycol) (PEG) and hydrophobic poly(γ-benzyl L-glutamate) (PBLG), was prepared as the potential carrier of doxorubicin (DOX) via a facile synthetic method in the presence of a shell-sheddable PEG macroinitiator (PEG-SS-NH2). Owing to its amphiphilic nature, the copolymer (PEG-SS-PBLG) formed spherical micelles (137 nm in diameter)in aqueous conditions. The micelles were stable under the physiologic condition (pH 7.4) and were readily cleaved in the presence of glutathione (GSH), a tripeptide reducing the disulfide bond in the cytoplasm of the cell. DOX,chosen as a model anticancer drug, was effectively encapsulated into the hydrophobic core of the micelle with high loading efficiency (>75%). The micelle released DOX completely within 18 h at 10 mM GSH mimicking the intracellular condition, whereas only 34% of the drug was released from the micelle at 2 μM GSH. In vitro cytotoxicity tests revealed that DOX-loaded reduction-sensitive micelles are more toxic to SCC7 cells than reduction-insensitive control micelles. These results suggest that PEG-SS-PBLG is the promising carrier for the intracellular delivery of DOX.