Pharmaceutical Research

, Volume 14, Issue 10, pp 1431–1436 | Cite as

Chitosan and Chitosan/Ethylene Oxide-Propylene Oxide Block Copolymer Nanoparticles as Novel Carriers for Proteins and Vaccines

  • Pilar Calvo
  • Carmen Remuñan-López
  • Jose Luis Vila-Jato
  • María José AlonsoEmail author


Purpose. The aim of this study was to investigate the interaction between the components of novel chitosan (CS) and CS/ethylene oxide-propylene oxide block copolymer (PEO-PPO) nanoparticles and to evaluate their potential for the association and controlled release of proteins and vaccines.

Methods. The presence of PEO-PPO on the surface of the nanoparticles and its interaction with the CS was identified by X-ray photoelectron spectroscopy (XPS). The mechanism of protein association was elucidated using several proteins, bovine serum albumin (BSA), and tetanus and diphtheria toxoids, and varying the formulation conditions (different pH values and concentrations of PEO-PPO), and the stage of protein incorporation into the nanoparticles formation medium.

Results. BSA and tetanus and diphtheria toxoids were highly associated with CS nanoparticles partly due to electrostatic interactions between the carboxyl groups of the protein and the amine groups of CS. PEO-PPO also interacted electrostatically with CS, thus competing with the proteins for association with CS nanoparticles. A visible amount of PEO-PPO was projected towards the outer phase of the nanoparticles. Proteins were released from the nanoparticles at an almost constant rate, the intensity of which was closely related to the protein loading. Furthermore, the tetanus vaccine was released in the active form for at least 15 days.

Conclusions. CS and CS/PEO-PPO nanoparticles prepared by a very mild ionic crosslinking technique are novel and suitable systems for the entrapment and controlled release of proteins and vaccines.

chitosan ethylene oxide-propylene oxide block copolymer nanoparticles vaccine delivery protein delivery ionic gelation 


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  1. 1.
    H. L. Lueßen, C. O. Rentel, A. F. Kotzé, C. M. Lehr, A. G. de Boer, J. C. Verhoef, and H. E. Junginger. J. Control. Rel. 45:15-23 (1997).Google Scholar
  2. 2.
    S. Kobayashi, S. Kondo, and K. Juni. Pharm. Res. 13:80-83 (1996).PubMedGoogle Scholar
  3. 3.
    H. P. Merkle, and G. Wolany. J. Control. Rel. 21:155-164 (1995).Google Scholar
  4. 4.
    J. C. Verhoef, N. G. M. Schipper, S. G. Romeijn, and F. W. H. M. Merkus. J. Control. Rel. 29:351-360 (1994).Google Scholar
  5. 5.
    D. T. O'Hagan, CRC Press, Boca Raton, 1994, pp 1-24.Google Scholar
  6. 6.
    E. Lipka, J. Crison, and G. L. Amidon. J. Control. Rel. 39:121-129 (1996).Google Scholar
  7. 7.
    D. A. Epstein, and J. P. Longenecker. Crit. Rev. Ther. Drug Carrier Syst. 5:99-139 (1988).PubMedGoogle Scholar
  8. 8.
    V. H. L. Lee, A. Yamamoto, and U. B. Kompelia. Crit. Rev. Ther. Drug Carrier Syst. 8:91-192 (1991).PubMedGoogle Scholar
  9. 9.
    P. Calvo, C. Remuñan-López, J. L. Vila-Jato, and M. J. Alonso. J. Appl. Polym. Sci. 63:125-132 (1997).Google Scholar
  10. 10.
    S. Hirano, H. Seino, Y. Akiyama, and I. Nonaka. Polym. Eng. Sci. 59:897-901 (1988).Google Scholar
  11. 11.
    L. Illum, N. F. Farraj, and S. S. Davis. Pharm. Res. 11:1186-1189 (1994).PubMedGoogle Scholar
  12. 12.
    G. Borchard, H. L. Lueßen, A. G. de Boer, J. Coss Verhoef, C. M. Lehr, and H. E. Junginger. J. Control. Rel. 39:131-138 (1996).Google Scholar
  13. 13.
    R. Bodmeier, K. Oh, and Y. Pramar. Drug Dev. Ind. Pharm. 15:1475-1494 (1989).Google Scholar
  14. 14.
    S. Shiraishi, T. Imai, and M. Otagiri. J. Control Rel. 25:217-225 (1993).Google Scholar
  15. 15.
    R. Bodmeier and O. Paeratakul. J. Pharm. Sci. 78:964-966 (1989).PubMedGoogle Scholar
  16. 16.
    R. Bodmeier, H. Chen, and O. Paeratakul. Pharm. Res. 6:413-417 (1989).PubMedGoogle Scholar
  17. 17.
    B.D. Ratner and B.J. McElroy. In R.M. Gendreau (ed.) Spectroscopy in the biomedical sciences, CRC Press, Boca Raton, FL, 1986, pp. 107-140.Google Scholar
  18. 18.
    K. Yao, T. Peng, M. F. A. Goosen, J. M. Min, and Y. Y. He. J. Applied Polymer Sci. 48:343-354 (1993).Google Scholar
  19. 19.
    H. Yoshida, H. Nishihara, and T. Kataoka. Biotech. Bioeng. 43:1087-1093 (1994).Google Scholar

Copyright information

© Plenum Publishing Corporation 1997

Authors and Affiliations

  • Pilar Calvo
    • 1
  • Carmen Remuñan-López
    • 1
  • Jose Luis Vila-Jato
    • 1
  • María José Alonso
    • 1
    Email author
  1. 1.Department of Pharmacy and Pharmaceutical Technology, School of PharmacyUniversity of Santiago de CompostelaSantiago de CompostelaSpain

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