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Glutathione-responsive gemini polymeric micelles as controlled drug carriers

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Abstract

Gemini poly(ethylene glycol)-cystine-poly(s-butyl cysteine) ((PEG)2-Cyt-(PBC)2) with a cystine disulfide bond as a spacer was prepared via oxidation of the cysteine group of monomeric poly(ethylene glycol)-cysteine-poly(s-butyl cysteine) (PEG-Cys-PBC) in solution, which is specifically cleavable in intracellular compartments. Due to its amphiphilic nature, (PEG)2-Cyt-(PBC)2 formed micelles under aqueous conditions; the average diameter of the micelles was 26.9 nm. The critical micelle concentration (CMC) of the polymer was 15.8 mg/L. The loading content of the chosen model drug, indomethacine (IMC), was much higher for gemini micelles than that for monomeric micelles. The (PEG)2-Cyt-(PBC)2 micelles released 75% of the loaded IMC within 72 h under 10 mM glutathione (GSH), whereas 36% of the loaded IMC was released from the micelles in the absence of GSH. An in vitro cytotoxicity experiment revealed that PTX-loaded gemini micelles showed toxicity to A549 cells with increasing GSH concentrations. Microscopic observation of gemini micelles demonstrated that the micelles containing a disulfide bond could effectively deliver the drug into A549 cells. These results suggest the potential of disulfide-based gemini polymeric micelles as controlled drug delivery carriers.

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Authors and Affiliations

  1. Nano & Bio Research Division, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, 711-873, Korea

    Hyun-Chul Kim, Eunjoo Kim, Sang Won Jeong, Se Guen Lee & Sung Jun Lee

  2. School of Chemical Engineering, Yeungnam University, Gyeongbuk, 712-749, Korea

    Seung Woo Lee

Authors
  1. Hyun-Chul Kim
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  2. Eunjoo Kim
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  3. Sang Won Jeong
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  4. Se Guen Lee
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  5. Sung Jun Lee
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  6. Seung Woo Lee
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Correspondence to Hyun-Chul Kim.

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The image from this article is used as the cover image of the Volume 23, Issue 2.

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Kim, HC., Kim, E., Jeong, S.W. et al. Glutathione-responsive gemini polymeric micelles as controlled drug carriers. Macromol. Res. 23, 196–204 (2015). https://doi.org/10.1007/s13233-015-3030-4

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  • DOI: https://doi.org/10.1007/s13233-015-3030-4

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