Macromolecular Research

, Volume 20, Issue 3, pp 250–258 | Cite as

Synthesis, characterization, and drug delivery of amphiphilic poly{(lactic acid)-co-[(glycolic acid)-alt-(L-glutamic acid)]}-g-poly(ethylene glycol)

  • Zuxiao Yu
  • Bin He
  • Chunyan Long
  • Rong Liu
  • Mingming Sheng
  • Gang Wang
  • James. Z. Tang
  • Zhongwei Gu


This paper discusses the use of a novel amphiphilic graft polymer poly{(lactic acid)-co-[(glycolic acid)-alt-(Lglutamic acid)]}-g-monomethyl poly(ethylene glycol) (PLGG-g-mPEG) as a drug carrier. PLGG was synthesized through the ring-opening polymerization of L-lactide (LLA) and (3s)-benzoxylcarbonylethyl-morpholine-2,5-dione (BEMD) using Sn(Oct)2 as a catalyst and it was subsequently deprotected via hydrogenolysis in the presence of Pd/C. A series of monomethyl poly(ethylene glycol) (PEG) with the molecular weights of 2,000, 1,100, and 500 were immobilized on the carboxyl groups of PLGG. These PEGylated graft derivatives were characterized using proton nuclear magnetic resonance spectra (1H NMR), Fourier transform infrared spectroscopy (FTIR), and gel permeation chromatography (GPC). The critical micelle concentrations (CMCs) of the amphiphilic copolymers were tested by the fluorescence probe technique and the CMCs were 2.3, 1.0, and 0.32 μg/mL, respectively. Transmission electronic microscopy (TEM) and dynamic light scattering (DLS) images revealed that the micelles were homogeneous spherical nanoparticles and the sizes of the micelles were distributed across a range of 80 to 22 nm. Anticancer drug doxorubicin (DOX) was loaded into the micelles. The in vitro release profiles showed that the sustaining release of the drugloaded micelles could last over 7 days. The in vitro cytotoxicity assay of the DOX-loaded micelles against HepG2 cells was assessed by methyl thiazolyl tetrazolium (MTT) assays. The results demonstrated that the drug-loaded micelles exhibited a high level of inhibition activity on cancer cells. The confocal microscopy images of HepG2 cells showed that DOX released from the micelles could be delivered into cell nuclei. PLGG-g-mPEG micelles are promising potential carriers for delivering anticancer drugs.


PLGG-g-mPEG micelles drug delivery doxorubicin (DOX) 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. (1).
    K. T. Oh, H. Yin, E. S. Lee, and Y. H. Bae, J. Mater. Chem., 17, 3987 (2007).CrossRefGoogle Scholar
  2. (2).
    E. S. Lee, K. Na, and Y. H. Bae, Nano Lett., 5, 325 (2005).CrossRefGoogle Scholar
  3. (3).
    K. T. Oh, Y. T. Oh, N. M. Oh, K. Kim, D. H. Lee, and E. S. Lee, Int. J. Pharm., 375, 163 (2009).CrossRefGoogle Scholar
  4. (4).
    P. S. Lai, P. J. Lou, C. L. Peng, C. L. Pai, W. N. Yen, M. Y. Huang, T. H. Young, and M. J. Shieh, J. Control. Release, 122, 39 (2007).CrossRefGoogle Scholar
  5. (5).
    H. L. Wong, R. Bendayan, A. M. Rauth, H. Y. Xue, K. Babakhanian, and X. Y. Wu, J. Pharmacol. Exp. Ther., 317, 1372 (2006).CrossRefGoogle Scholar
  6. (6).
    S. Ganta, H. Devalapally, A. Shahiwala, and M. Amiji, J. Control. Release, 126, 187 (2008).CrossRefGoogle Scholar
  7. (7).
    J. O. Kim, A. V Kabanov, and T. K. Bronich, J. Control. Release, 138, 197 (2009).CrossRefGoogle Scholar
  8. (8).
    X. B. Xiong, Z. Ma, R. Lai, and A. Lavasanifar, Biomaterials, 31, 757 (2009).CrossRefGoogle Scholar
  9. (9).
    W. I. Ganz, K. S. Sridhar, S. S. Ganz, R. Gonzalez, S. Chakko, and A. Serafini, Oncology, 53, 461 (1996).CrossRefGoogle Scholar
  10. (10).
    M. Ceruti, P. Crosasso, P. Brusa, S. Arpicco, F. Dosio, and L. Cattel, J. Control. Release, 63, 141 (2000).CrossRefGoogle Scholar
  11. (11).
    D. Chen and K. H. Lee, Biochim. Biophys. Acta, 1158, 244 (1993).CrossRefGoogle Scholar
  12. (12).
    J. Huwyler, D. Wu, and W. M. Pardridge, Proc. Natl. Acad. Sci. U.S.A., 93, 14164 (1996).CrossRefGoogle Scholar
  13. (13).
    X. Zhou and L. Huang, J. Control. Release, 19, 269 (1992).CrossRefGoogle Scholar
  14. (14).
    R. Ideta, F. Tasaka, W. D. Jang, N. Nishiyama, G. D. Zhang, A. Harada, Y. Yanagi, Y. Tamaki, T. Aida, and K. Kataoka, Nano. Lett., 5, 2426 (2005).CrossRefGoogle Scholar
  15. (15).
    W. D. Jang, Y. Nakagishi, N. Nishiyama, S. Kawauchi, Y. Morimoto, M. Kikuchi, and K. Kataoka, J. Control. Release, 113, 73 (2006).CrossRefGoogle Scholar
  16. (16).
    J. Kopecek, P. Kopeckova, T. Minko, Z. R. Lu, and C. M. Peterson, J. Control. Release, 74, 147 (2001).CrossRefGoogle Scholar
  17. (17).
    P. Kan, Z. B. Chen, C. J. Lee, and I. M. Chu, J. Control. Release, 58, 271 (1999).CrossRefGoogle Scholar
  18. (18).
    A. Niethammer, G. Gaedicke, H. N. Lode, and W. Wrasidlo, Bioconjug. Chem., 12, 414 (2001).CrossRefGoogle Scholar
  19. (19).
    W. Wrasidlo, G. Gaedicke, R. K. Guy, J. Renaud, P. Emmanuel, K. C. Nicolaou, R. A. Reisfeld, and H. N. Lode, Bioconjug. Chem., 13, 1093 (2002).CrossRefGoogle Scholar
  20. (20).
    A. Gabizon, H. Shmeeda, and Y. Barenholz, Clin Pharmacokinet., 42, 419 (2003).CrossRefGoogle Scholar
  21. (21).
    A. S. Mikhail and C. Allen, J. Control. Release, 138, 214 (2009).CrossRefGoogle Scholar
  22. (22).
    A. Lavasanifar, J. Samuel, and G. S. Kwon, Adv. Drug Deliv. Rev., 54, 169 (2002).CrossRefGoogle Scholar
  23. (23).
    X. T. Shuai, T. Merdan, A. K. Schaper, F. Xi, and T. Kissel, Bioconjug. Chem., 15, 441 (2004).CrossRefGoogle Scholar
  24. (24).
    V. P. Torchilin, Cell Mol. Life Sci., 61, 2549 (2004).CrossRefGoogle Scholar
  25. (25).
    K. Kataoka, A. Harada, and Y. Nagasaki, Adv. Drug Deliv. Rev., 47, 113 (2001).CrossRefGoogle Scholar
  26. (26).
    H. Liu, S. Farrell, and K. Uhrich, J. Control. Release, 68, 167 (2000).CrossRefGoogle Scholar
  27. (27).
    A. Lavasanifar, J. Samuel, and G. S. Kwon, Adv. Drug Deliv. Rev., 54, 169 (2002).CrossRefGoogle Scholar
  28. (28).
    H. Maeda, Adv. Enzyme Regul., 41, 189 (2001).CrossRefGoogle Scholar
  29. (29).
    H. Maeda, J. Wu, T. Sawa, Y. Matsumura, and K. Hori, J. Control. Release, 65, 271 (2000).CrossRefGoogle Scholar
  30. (30).
    Y. Matsumura and H. Maeda, Cancer Res., 6, 6387 (1986).Google Scholar
  31. (31).
    N. Rapoport, Z. Gao, and A. Kennedy, J. Natl. Cancer Inst., 99, 1095 (2007).CrossRefGoogle Scholar
  32. (32).
    G. Gaucher, M. H. Dufresne, V. P. Sant, N. Kang, D. Maysinger, and J. C. Leroux, J. Control. Release, 109, 169 (2005).CrossRefGoogle Scholar
  33. (33).
    D. A. Barrera, E. Zylstra, P. T. Lansbury, and R. Langer, J. Am. Chem. Soc., 115, 11010 (1993).CrossRefGoogle Scholar
  34. (34).
    T. Ouchi, T. Nozaki, A. Ishikawa, I. Fujimoto, and Y. Ohya, J. Polym. Sci. Part A: Polym. Chem., 35, 377 (1997).CrossRefGoogle Scholar
  35. (35).
    T. Ouchi, M. Sasakawa, H. Arimura, M. Toyohara, and Y. Ohya, Polymer, 45, 1583 (2004).CrossRefGoogle Scholar
  36. (36).
    T. Ouchi, H. Miyazaki, H. Arimura, F. Tasaka, A. Hamada, and Y. Ohya, J. Polym. Sci. Part A: Polym. Chem., 40, 1426 (2002).CrossRefGoogle Scholar
  37. (37).
    T. Ouchi, T. Nozaki, Y. Okamoto, M. Shiratani, and Y. Ohya, Macromol. Chem. Phys., 197, 1823 (1996).CrossRefGoogle Scholar
  38. (38).
    X. M. Deng, J. R. Yao, M. L. Yuan, X. H. Li, and C. D. Xiong, Macromol. Chem. Phys., 201, 2371 (2000).CrossRefGoogle Scholar
  39. (39).
    H. L. Guan, Z. G. Xie, P. B. Zhang, C. Deng, X. S. Chen, and X. B. Jing, Biomacromolecules, 6, 1954 (2005).CrossRefGoogle Scholar
  40. (40).
    Z. G. Xie, H. L. Guan, X. S. Chen, C. H. Lu, L. Chen, X. L. Hu, Q. Shi, and X. B. Jing, J. Control. Release, 117, 210 (2007).CrossRefGoogle Scholar
  41. (41).
    C. H. Lu, X. S. Chen, Z. G. Xie, T. C. Lu, X. Wang, J. Ma, and X. B. Jing, Biomacromolecules, 7, 1806 (2006).CrossRefGoogle Scholar
  42. (42).
    Y. Feng, D. Klee, H. Keul, and H. Höcker, Macromol. Biosci., 1, 30 (2001).CrossRefGoogle Scholar
  43. (43).
    W. W. Tian, Q. Chen, C. H. Yu, and J. Shen, Eur. Polym. J., 39, 1935 (2003).CrossRefGoogle Scholar
  44. (44).
    E. S. Lee, K. Na, and Y. H. Bae, J. Control. Release, 103, 405 (2005).CrossRefGoogle Scholar
  45. (45).
    B. He, J. Z. Bei, and S. G. Wang, Polymer, 44, 989 (2003).CrossRefGoogle Scholar
  46. (46).
    J. X. Zhang, L. Y. Qiu, Y Jin, and K. J. Zhu, React. Funct. Polym., 66, 1630 (2006).CrossRefGoogle Scholar
  47. (47).
    T. H. Kim, C. W. Mount, W. R. Gombotz, and S. H. Pun, Biomaterials, 31, 7386 (2010).CrossRefGoogle Scholar
  48. (48).
    E. V. Batrakova, S. Li, Y. L. Li, V. Y. Alakhov, W. F. Elmquist, and A. V. Kabanov, J. Control. Release, 100, 389 (2004).CrossRefGoogle Scholar
  49. (49).
    H. L. Wong, R. Bendayan, A. M. Rauth, H. Y. Xue, K. Babakhanian, and X. Y. Wu, J. Pharmacol. Exp. Ther., 317, 1372 (2006).CrossRefGoogle Scholar
  50. (50).
    H. Chen, S. Kim, L. Li, S. Wang, K. Park, and J. X. Cheng, Proc. Natl. Acad. Sci. U.S.A., 105, 6596 (2008).CrossRefGoogle Scholar

Copyright information

© The Polymer Society of Korea and Springer Netherlands 2012

Authors and Affiliations

  • Zuxiao Yu
    • 1
    • 2
  • Bin He
    • 1
  • Chunyan Long
    • 1
  • Rong Liu
    • 1
  • Mingming Sheng
    • 1
  • Gang Wang
    • 1
  • James. Z. Tang
    • 3
  • Zhongwei Gu
    • 1
  1. 1.National Engineering Research Center for BiomaterialsSichuan UniversityChengduP. R. China
  2. 2.College of Material and Chemical EngineeringSichuan University of Science & EngineeringZigongP. R. China
  3. 3.Department of Pharmacy, School of Applied SciencesUniversity of WolverhamptonWolverhamptonUK

Personalised recommendations