화학공학소재연구정보센터
홈 로그인 로그아웃 연락처 사이트맵
Macromolecular Research, Vol.23, No.2, 196-204, February, 2015
DOI10.1007/s13233-015-3030-4  Export Citation
Glutathione-responsive gemini polymeric micelles as controlled drug carriers
Hyun-Chul Kim†, Eunjoo Kim, Sang Won Jeong, Se Guen Lee, Sung Jun Lee, and Seung Woo Lee1
  • Nano & Bio Research Division, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, 711-873, Korea
  • 1School of Chemical Engineering, Yeungnam University, Gyeongbuk, 712-749, Korea
E-mail:
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.
Keywords:gemini surfactants;drug delivery system;polypeptide;disulfide-thiol exchange;stimuli-sensitive polymers
  1. Zhang LF, Eisenberg A, J. Am. Chem. Soc., 118(13), 3168 (1996)
  2. Rank A, Hauschild S, Forster S, Schubert R, Langmuir, 25(3), 1337 (2009)
  3. Kita-Tokarczyk K, Grumelard J, Haefele T, Meier W, Polymer, 46(11), 3540 (2005)
  4. Kataoka K, Harada A, Nagasaki Y, Adv. Drug Deliv. Rev., 47, 113 (2001)
  5. Torchilin VP, J. Control. Release, 73, 137 (2001)
  6. Gaucher G, Dufresne MH, Sant VP, Kang N, Maysinger D, Leroux JC, J. Control. Release, 109, 169 (2005)
  7. Rapoport N, Prog. Polym. Sci., 32, 962 (2007)
  8. Lavasanifar A, Samuel J, Kwon GS, Adv. Drug Deliv. Rev., 54, 169 (2002)
  9. Moghimi SM, Hunter AC, Murray JC, Pharmacol. Rev., 53, 283 (2001)
  10. Hagan SA, Coombes AG, Garnett MC, Dunn SE, Davis MC, Illum L, Davis SS, Harding SE, Purkiss S, Gellert PR, Langmuir, 12(9), 2153 (1996)
  11. Kim SY, Kim JH, Kim D, An JH, Lee DS, Kim SC, J. Appl. Polym. Sci., 82(10), 2599 (2001)
  12. Kim SY, Shin IG, Lee YM, Biomaterials, 20, 1033 (1999)
  13. Avgoustakisa K, Beletsia A, Panagia Z, Klepetsanisa P, Karydasb AG, Ithakissios DS, J. Control. Release, 79, 123 (2002)
  14. Allen C, Han J, Yu Y, Maysinger D, Eisenberg A, J. Control. Release, 63, 275 (2000)
  15. Carlsen A, Lecommandoux S, Curr. Opin. Colloid Interface Sci., 14, 329 (2009)
  16. Arimura H, Ohya Y, Ouchi T, Biomacromolecules, 6(2), 720 (2005)
  17. Checot F, Brulet A, Oberdisse J, Gnanou Y, Mondain-Monval O, Lecommandoux S, Langmuir, 21(10), 4308 (2005)
  18. Gebhardt KE, Ahn S, Venkatachalam G, Savin DA, Langmuir, 23(5), 2851 (2007)
  19. Kwon GS, Naito M, Yokoyama M, Okano T, Sakurai Y, Kataoka K, Langmuir, 9, 945 (1993)
  20. Jeong YI, Cheon JB, Kim SH, Nah JW, Lee YM, Sung YK, Akaike T, Cho CS, J. Control. Release, 51, 169 (1998)
  21. Wang W, Tetley L, Uchegbu IF, Langmuir, 16(20), 7859 (2000)
  22. Lee ES, Shin HJ, Na K, Bae YH, J. Control. Release, 90, 363 (2003)
  23. Sun J, Chen XS, Lu TC, Liu S, Tian HY, Guo ZP, Jing XB, Langmuir, 24(18), 10099 (2008)
  24. Wong SM, Cha JN, Choi KS, Deming TJ, Stucky GD, Nano Lett., 2, 583 (2002)
  25. Bromberg L, Levin G, Bioconjug. Chem., 9, 40 (1998)
  26. Zugates GT, Anderson DG, Little SR, Lawhorn IEB, Langer R, J. Am. Chem. Soc., 128(39), 12726 (2006)
  27. Zana R, J. Colloid Interface Sci., 248(2), 203 (2002)
  28. Paddon-Jones G, Regismond S, Kwetkat K, Zana R, J. Colloid Interface Sci., 243(2), 496 (2001)
  29. Tehrani-Bagha AR, Singh RG, Holmberg K, J. Colloid Interface Sci., 376, 112 (2012)
  30. Dreja M, Pyckhout-Hintzen W, Mays H, Tieke B, Langmuir, 15(2), 391 (1999)
  31. Choi T, Shimizu Y, Shirai H, Hamada K, Dyes Pigment, 45, 145 (2000)
  32. Kim HC, Kim E, Lee SG, Lee SJ, Kim H, Jeong SW, J. Polym. Sci. A: Polym. Chem., 52(4), 582 (2014)
  33. Saito G, Swanson JA, Lee KD, Adv. Drug Deliv. Rev., 55, 199 (2003)
  34. Sun KH, Sohn YS, Jeong B, Biomacromolecules, 10, 2871 (2006)
  35. Sin L, Liu W, Dong CM, Chem. Commun., 47, 11282 (2011)
  36. Cunningham A, Oh JK, Macromol. Rapid Commun., 34(2), 163 (2013)
  37. Liu JY, Pang Y, Huang W, Huang XH, Meng LL, Zhu XY, Zhou YF, Yan DY, Biomacromolecules, 12(5), 1567 (2011)
  38. Thambi T, Saravanakumar G, Chu JU, Heo R, Ko H, Deepagan VG, Kim JH, Park JH, Macromol. Res., 21(1), 100 (2013)
  39. Nahain AA, Nam JA, Mok H, Lee YK, Park SY, Macromol. Res., 21(1), 92 (2013)
  40. Koo AN, Rim HP, Park DJ, Kim JH, Jeong SY, Lee SC, Macromol. Res., 21(7), 809 (2013)
  41. Nam K, Park JW, Bark H, Han J, Nah JW, Jang MK, Kim SW, Macromol. Res., 22(4), 370 (2014)
  42. Xie Z, Guan H, Chen L, Tian H, Chen X, Jing X, Polymer, 46, 10523 (2006)
  43. Chung TW, Cho KY, Lee HC, Nah JW, Yeo JH, Akaike T, Cho CS, Polymer, 45(5), 1591 (2004)
  44. Kim KH, Lee JC, Lee J, Macromol. Biosci., 8, 339 (2008)
  45. Koo AN, Lee HJ, Kim SE, Chang JH, Park C, Kim C, Park JH, Lee SC, Chem. Commun.
  46. Sun HL, Guo BN, Li XQ, Cheng R, Meng FH, Liu HY, Zhong ZY, Biomacromolecules, 11(4), 848 (2010)
  47. Ryu JH, Roy R, Ventura J, Thayumanavan S, Langmuir, 26(10), 7086 (2010)