Synthesis and physicochemical characterization of reduction-sensitive block copolymer for intracellular delivery of doxorubicin

Thavasyappan Thambi, Gurusamy Saravanakumar, Jun Uk Chu, Roun Heo, Hyewon Ko, Veerasikku Gopal Deepagan, Jong Ho Kim, Jae Hyung Park

Research output: Contribution to journalArticleResearchpeer-review

33 Citations (Scopus)

Abstract

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-NH 2 ). 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 μM 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.

Original languageEnglish
Pages (from-to)100-107
Number of pages8
JournalMacromolecular Research
Volume21
Issue number1
DOIs
Publication statusPublished - 1 Jan 2013
Externally publishedYes

Keywords

  • Amphiphilic block copolymer
  • Doxorubicin.
  • Glutathione
  • Reduction-sensitive micelle

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