Glutathione-responsive gemini polymeric micelles as controlled drug carriers

Hyun Chul Kim; Eunjoo Kim; Sang Won Jeong; Se Guen Lee; Sung Jun Lee; Seung Woo Lee

doi:10.1007/s13233-015-3030-4

Glutathione-responsive gemini polymeric micelles as controlled drug carriers

Hyun Chul Kim, Eunjoo Kim, Sang Won Jeong, Se Guen Lee, Sung Jun Lee, Seung Woo Lee

Yeungnam University

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

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.

[Figure not available: see fulltext.]

Original language	English
Pages (from-to)	196-204
Number of pages	9
Journal	Macromolecular Research
Volume	23
Issue number	2
DOIs	https://doi.org/10.1007/s13233-015-3030-4
State	Published - Feb 2015

Bibliographical note

Publisher Copyright:
© 2015, The Polymer Society of Korea and Springer Sciene+Business Media Dordrecht.

Keywords

disulfide-thiol exchange
drug delivery system
gemini surfactants
polypeptide
stimuli-sensitive polymers

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10.1007/s13233-015-3030-4

Cite this

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title = "Glutathione-responsive gemini polymeric micelles as controlled drug carriers",

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.[Figure not available: see fulltext.]",

keywords = "disulfide-thiol exchange, drug delivery system, gemini surfactants, polypeptide, stimuli-sensitive polymers",

author = "Kim, {Hyun Chul} and Eunjoo Kim and Jeong, {Sang Won} and Lee, {Se Guen} and Lee, {Sung Jun} and Lee, {Seung Woo}",

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T1 - Glutathione-responsive gemini polymeric micelles as controlled drug carriers

AU - Kim, Hyun Chul

AU - Kim, Eunjoo

AU - Jeong, Sang Won

AU - Lee, Se Guen

AU - Lee, Sung Jun

AU - Lee, Seung Woo

PY - 2015/2

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N2 - 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.[Figure not available: see fulltext.]

AB - 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.[Figure not available: see fulltext.]

KW - disulfide-thiol exchange

KW - drug delivery system

KW - gemini surfactants

KW - polypeptide

KW - stimuli-sensitive polymers

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JO - Macromolecular Research

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ER -

Glutathione-responsive gemini polymeric micelles as controlled drug carriers

Abstract

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Keywords

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