Journal of Materials Science: Materials in Medicine

, Volume 19, Issue 12, pp 3525–3533 | Cite as

PEG-grafted chitosan nanoparticles as an injectable carrier for sustained protein release

  • X. G. Zhang
  • D. Y. Teng
  • Z. M. Wu
  • X. Wang
  • Z. Wang
  • D. M. Yu
  • C. X. Li


The development of injectable nanoparticulate “stealth” carriers for protein delivery is a major challenge. The objective of this work was to investigate the possibility of achieving the controlled release of a model protein, insulin, from PEG-grafted chitosan (PEG-g-chitosan) nanoparticles (mean diameter 150–300 nm) prepared by the ion gelation method. Insulin was efficiently incorporated into the nanoparticles, and reached as high as 38%. In vitro release showed that it could control the insulin release by choosing the composition, loading and release temperature. We observed that the composition of the nanoparticle surface (C/O ratio) increased from 2.40 to 3.23, with an increase in the incubation time. Therefore, we concluded that during this time, insulin release from PEG-g-chitosan nanoparticles followed a diffusion mechanism in which erosion was negligible. The experiments also demonstrated that PEG-g-chitosan helped to maintain the natural structure of the protein entrapped in the nanoparticles.


Chitosan Insulin Release Chitosan Nanoparticles Ionic Gelation Chitosan Chain 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The starting projects for young teachers from the Ministry of Education, for financial support are gratefully acknowledged.


  1. 1.
    R. Langer, Acc. Chem. Res. 33, 94 (2000). doi: 10.1021/ar9800993 CrossRefGoogle Scholar
  2. 2.
    E. Allemann, R. Gurny, E. Deolker, Eur. J. Pharm. Biopharm. 39, 173 (1993)Google Scholar
  3. 3.
    S. Hirano, H. Seino, Y. Akiyama, I. Nonaka, Polym. Eng. Sci. 59, 897 (1988)Google Scholar
  4. 4.
    K.A. Janes, P. Calvo, M.J. Alonso, Adv. Drug. Deliv. Rev. 47, 83 (2001). doi: 10.1016/S0169-409X(00)00123-X CrossRefGoogle Scholar
  5. 5.
    R. Fernández-Urrusuno, P. Calvo, C. Remuñan-Lopez, J.L. Vila-Jato, M.J. Alonso, Pharm. Res. 16, 1576 (1999). doi: 10.1023/A:1018908705446 CrossRefGoogle Scholar
  6. 6.
    A. Grenha, C.I. Grainger, L.A. Dailey, B. Seijo, G.P. Martin, C. Remuñán-López et al., Eur. J. Pharm. Sci. 31, 73 (2007). doi: 10.1016/j.ejps.2007.02.008 CrossRefGoogle Scholar
  7. 7.
    M.M. Amiji, Carbohyd. Polym. 32, 193 (1997). doi: 10.1016/S0144-8617(97)00006-4 CrossRefGoogle Scholar
  8. 8.
    D. Fischer, Y. Li, B. Ahlemeyer, J. Krieglstein, T. Kissel, Biomaterials 24, 1121 (2003). doi: 10.1016/S0142-9612(02)00445-3 CrossRefGoogle Scholar
  9. 9.
    S. Sagnella, K. Mai-Ngam, Colloids. Surf. B Biointerfaces 42, 147 (2005). doi: 10.1016/j.colsurfb.2004.07.001 CrossRefGoogle Scholar
  10. 10.
    R. Gerf, Y. Minamitake, M.T. Perracchia, V. Trubetskoy, V. Torchilin, R. Langer, Science 263, 1600 (1994). doi: 10.1126/science.8128245 CrossRefGoogle Scholar
  11. 11.
    P. Quellec, R. Gref, L. Perrin, E. Dellacherie, F. Sommer, J.M. Verbavatz et al., J. Biomed. Mater. Res. 42, 45 (1998). doi :10.1002/(SICI)1097-4636(199810)42:1<45::AID-JBM7>3.0.CO;2-OCrossRefGoogle Scholar
  12. 12.
    H. Otsuka, Y. Nagasaki, K. Kataoka, Adv. Drug. Deliv. Rev. 55, 403 (2003). doi: 10.1016/S0169-409X(02)00226-0 CrossRefGoogle Scholar
  13. 13.
    Y. Hu, X.Q. Jiang, Y. Ding, L.Y. Zhang, C.Z. Yang, J.F. Zhang et al., Biomaterials 24, 2395 (2003). doi: 10.1016/S0142-9612(03)00021-8 CrossRefGoogle Scholar
  14. 14.
    N. Bhattarai, H.R. Ramay, J. Gunn, F.A. Matsen, M.Q. Zhang, J. Control Release 103, 609 (2005). doi: 10.1016/j.jconrel.2004.12.019 CrossRefGoogle Scholar
  15. 15.
    Y.Q. Hu, H.L. Jiang, C.N. Xu, Y.J. Wang, K.J. Zhu, Carbohyd. Polym. 61, 472 (2005). doi: 10.1016/j.carbpol.2005.06.022 CrossRefGoogle Scholar
  16. 16.
    X. Jiang, H. Dai, K.W. Leong, S.H. Goh, H.Q. Mao, Y.Y. Yang, J. Gene. Med. 8, 477 (2006). doi: 10.1002/jgm.868 CrossRefGoogle Scholar
  17. 17.
    C. Prego, D. Torres, E. Fernandez-Megia, R. Novoa-Carballal, E. Quiñoá, M.J. Alonso, J. Control. Release 111, 299 (2006). doi: 10.1016/j.jconrel.2005.12.015 CrossRefGoogle Scholar
  18. 18.
    S.R. Mao, O. Germershaus, D. Fischer, T. Linn, R. Schnepf, T. Kissel, Pharm. Res. 22, 2058 (2005). doi: 10.1007/s11095-005-8175-y CrossRefGoogle Scholar
  19. 19.
    J.M. Harris, E.C. Struck, M.G. Case, M.S. Paley, M. Yalpani, J.M. Van Alstine et al., J. Polym. Sci. Polym. Chem. Ed. 22, 341 (1984). doi: 10.1002/pol.1984.170220207 CrossRefGoogle Scholar
  20. 20.
    S. Sajeesh, C.P. Sharma, J. Biomed. Mater. Res. B Appl. Biomater. 76, 298 (2006). doi: 10.1002/jbm.b.30372 Google Scholar
  21. 21.
    P. LinksCalvo, C. Remuñan-López, J.L. Vila-Jato, M.J. Alonso, Pharm. Res. 14, 1431 (1997). doi: 10.1023/A:1012128907225
  22. 22.
    T. Kaneko, K. Hamada, M.Q. Chen, M. Akashi, Macromolecules 37, 501 (2004). doi: 10.1021/ma035276g CrossRefGoogle Scholar
  23. 23.
    M. Huang, E. Khor, L.Y. Lim, Pharm. Res. 21, 344 (2004). doi: 10.1023/B:PHAM.0000016249.52831.a5 CrossRefGoogle Scholar
  24. 24.
    F. Kong, C.G. Ou, Y. Zheng, S.Y. Zhang, C.Z. Yang, X.L. Wu et al., J. Appl. Polym. Sci. 99, 2477 (2006). doi: 10.1002/app.22842 CrossRefGoogle Scholar
  25. 25.
    Q.H. Li, T. Yamashita, K. Horie, H. Yoshimoto, T. Miwa, Y. Maekawa, J. Polym. Sci. A Polym. Chem. 36, 1329 (1998). doi :10.1002/(SICI)1099-0518(199806)36:8<1329::AID-POLA16>3.0.CO;2-8CrossRefGoogle Scholar
  26. 26.
    L. Nielsen, S. Frokjaer, J. Carpenter, J. Brange, J. Pharm. Sci. 90, 29 (2001). doi :10.1002/1520-6017(200101)90:1<29::AID-JPS4>3.0.CO;2-4CrossRefGoogle Scholar
  27. 27.
    L. Jøgensen, C. Vermehren, S. Bjerregaard, S. Froekjaer, Int. J. Pharm. 254, 7 (2003). doi: 10.1016/S0378-5173(02)00668-3 CrossRefGoogle Scholar
  28. 28.
    B. Sarmento, D.C. Ferreira, L. Jorgensen, M. van de Weert, Eur. J. Pharm. Biopharm. 65, 10 (2007). doi: 10.1016/j.ejpb.2006.09.005 CrossRefGoogle Scholar
  29. 29.
    Y. Pocker, B. Subhasis, Biswas Biochem. 19, 5043 (1980). doi: 10.1021/bi00563a017 Google Scholar
  30. 30.
    V.R. Sinha, A.K. Singla, S. Wadhawan, R. Kaushik, R. Kumria, K. Bansal et al., Int. J. Pharm. 274, 1 (2004). doi: 10.1016/j.ijpharm.2003.12.026 CrossRefGoogle Scholar
  31. 31.
    A. Portero, D. Teijeiro-Osorio, M.J. Alonso, C. Remuñán-López, Carbohyd. Polym. 68, 617 (2007). doi: 10.1016/j.carbpol.2006.07.028 CrossRefGoogle Scholar
  32. 32.
    S.Q. Liu, Y.Y. Yang, X.M. Liu, Y.W. Tong, Biomacromolecules 4, 1784 (2003). doi: 10.1021/bm034189t CrossRefGoogle Scholar
  33. 33.
    B. Jeong, S.W. Kim, Y.H. Bae, Adv. Drug. Deliv. Rev. 54, 37 (2002). doi: 10.1016/S0169-409X(01)00242-3 CrossRefGoogle Scholar
  34. 34.
    A. Chenite, C. Chaput, D. Wang, C. Combes, M.D. Buschmann, C.D. Hoemann et al., Biomaterials 21, 2155 (2000). doi: 10.1016/S0142-9612(00)00116-2 CrossRefGoogle Scholar
  35. 35.
    F. Rosso, A. Barbarisi, M. Barbarisi, A. Giordano, J. Mater. Sci. Mater. Med. 15, 679 (2004)CrossRefGoogle Scholar
  36. 36.
    G. Beamson, B.T. Pickup, W. Li, S.M. Mai, J. Phys. Chem. B 104, 2656 (2000). doi: 10.1021/jp9905629 CrossRefGoogle Scholar
  37. 37.
    G. Lawrie, I. Keen, B. Drew, A. Chandler-Temple, L. Rintoul, P. Fredericks et al., Biomacromolecules 8, 2533 (2007). doi: 10.1021/bm070014y CrossRefGoogle Scholar
  38. 38.
    L.Y. Li, S.F. Chen, J. Zheng, B.D. Ratner, S.Y. Jiang, J. Phys. Chem. B 109, 2934 (2005). doi: 10.1021/jp0473321 CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  1. 1.Key Laboratory of Functional Polymer Materials, Ministry Education, and Institute of Polymer ChemistryNankai UniversityTianjinChina
  2. 2.Metabolic Diseases HospitalTianjin Medical UniversityTianjinChina

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