Skip to main content
SpringerLink
Log in

Tumor targeting and pH-responsive polyelectrolyte complex nanoparticles based on hyaluronic acid-paclitaxel conjugates and Chitosan for oral delivery of paclitaxel

  • Articles
  • Published:
Macromolecular Research Aims and scope Submit manuscript

Abstract

A new platform of paclitaxel (PTX) for application as an oral delivery system was developed, by combining the pH sensitivity of polyelectrolyte complex nanoparticles (CNPs) and the active targeting of hyaluronic acid (HA). Chitosan/hyaluronic acid-paclitaxel (CS/HA-PTX) CNPs were prepared by coating the CS onto the HA-PTX nanoparticles (NPs), and characterized by Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (1H NMR), transmission electron microscopy (TEM) and high-performance liquid chromatography (HPLC). HA-PTX conjugates could self-assemble into NPs in aqueous solution with an average size of 100±5 nm, and the PTX content of HA-PTX conjugates was 10.6 wt%. The CS/HA-PTX CNPs had a smaller size and higher PTX content when the ratio of positive charge to negative charge was 2:1. The in vitro release of PTX from CNPs was pH-responsive, suggesting that the CS shell could prevent the breakage of the ester bond in HA-PTX NPs in acidic pH conditions. HA-PTX NPs exhibited higher cellular uptake than free PTX against HepG2 cells via receptor-mediated endocytosis. PTX could accumulate remarkably into tumor sites after oral administration of CNPs. These results indicate that the CNP drug delivery system has great potential for applications in the oral administration of hydrophobic drugs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. L. Bromberg, J. Control. Release, 128, 99 (2008).

    Article  CAS  Google Scholar 

  2. Y.-H. Lin, H.-F. Liang, C.-K. Chung, M.-C. Chen, and H.-W. Sung, Biomaterials, 26, 2105 (2005).

    Article  CAS  Google Scholar 

  3. Y.-H. Lin, F.-L. Mi, C.-T. Chen, W.-C. Chang, S.-F. Peng, H.-F. Liang, and H.-W. Sung, Biomacromolecules, 8, 146 (2007).

    Article  CAS  Google Scholar 

  4. G. Gaucher, P. Satturwar, M.-C. Jones, A. Furtos, and J.-C. Leroux, Eur. J. Pharm. Biopharm., 76, 147 (2010).

    Article  CAS  Google Scholar 

  5. L. M. Ensign, R. Cone, and J. Hanes, Adv. Drug Deliv. Rev., 64, 557 (2012).

    Article  CAS  Google Scholar 

  6. F. Leonelli, A. La Bella, L. Migneco, and R. Bettolo, Molecules, 13, 360 (2008).

    Article  CAS  Google Scholar 

  7. M. M. Malingre, J. H. Beijnen, and J. H. M. Schellens, Invest. New Drugs, 19, 155 (2001).

    Article  CAS  Google Scholar 

  8. P. Breedveld, J. H. Beijnen, and J. H. M. Schellens, Trends Pharmacol. Sci., 27, 17 (2006).

    Article  CAS  Google Scholar 

  9. C. Fonseca, S. Simoes, and R. Gaspar, J. Control. Release, 83, 273 (2002).

    Article  CAS  Google Scholar 

  10. L. Vicari, T. Musumeci, I. Giannone, L. Adamo, C. Conticello, R. De Maria, R. Pignatello, G. Puglisi, and M. Gulisano, BMC Cancer, 8 (2008).

  11. G. Bachar, K. Cohen, R. Hod, R. Feinmesser, A. Mizrachi, T. Shpitzer, O. Katz, and D. Peer, Biomaterials, 32, 4840 (2011).

    Article  CAS  Google Scholar 

  12. I. Rivkin, K. Cohen, J. Koffler, D. Melikhov, D. Peer, and R. Margalit, Biomaterials, 31, 7106 (2010).

    Article  CAS  Google Scholar 

  13. H. Lee, C.-H. Ahn, and T.G. Park, Macromol. Biosci., 9, 336 (2009).

    Article  CAS  Google Scholar 

  14. D. Yang, X. Liu, X. Jiang, Y. Liu, W. Ying, H. Wang, H. Bai, W. D. Taylor, Y. Wang, J.-P. Clamme, E. Co, P. Chivukula, K. Y. Tsang, Y. Jin, and L. Yu, J. Control. Release, 161, 124 (2012).

    Article  CAS  Google Scholar 

  15. Y. J. Jun, J. H. Min, D. E. Ji, J. H. Yoo, J. H. Kim, H. J. Lee, B. Jeong, and Y. S. Sohn, Bioorg. Med. Chem. Lett., 18, 6410 (2008).

    Article  CAS  Google Scholar 

  16. D. Kalaria, G. Sharma, V. Beniwal, and M. R. Kumar, Pharm. Res., 26, 492 (2009).

    Article  CAS  Google Scholar 

  17. E. Lee, J. Lee, I.-H. Lee, M. Yu, H. Kim, S. Y. Chae, and S. Jon, J. Med. Chem., 51, 6442 (2008).

    Article  CAS  Google Scholar 

  18. L. Milas, K. A. Mason, N. Hunter, C. Li, and S. Wallace, Int. J. Radiat. Oncol., 55, 707 (2003).

    Article  CAS  Google Scholar 

  19. E. Lee, H. Kim, I.-H. Lee, and S. Jon, J. Control. Release, 140, 79 (2009).

    Article  CAS  Google Scholar 

  20. X. Zhang, Y. Li, X. Chen, X. Wang, X. Xu, Q. Liang, J. Hu, and X. Jing, Biomaterials, 26, 2121 (2005).

    Article  CAS  Google Scholar 

  21. C. Li, R. A. Newman, Q. P. Wu, S. Ke, W. Chen, T. Hutto, Z. X. Kan, M. D. Brannan, C. Charnsangavej, and S. Wallace, Cancer Chemother. Pharmacol., 46, 416 (2000).

    Article  CAS  Google Scholar 

  22. A. K. Jain, N. K. Swarnakar, C. Godugu, R. P. Singh, and S. Jain, Biomaterials, 32, 503 (2011).

    Article  CAS  Google Scholar 

  23. C. E. Schante, G. Zuber, C. Herlin, and T. F. Vandamme, Carbohydr. Polym., 85, 469 (2011).

    Article  CAS  Google Scholar 

  24. I. De Stefano, A. Battaglia, G. F. Zannoni, M. G. Prisco, A. Fattorossi, D. Travaglia, S. Baroni, D. Renier, G. Scambia, C. Ferlini, and D. Gallo, Cancer Chemother. Pharmacol., 68, 107 (2011).

    Article  CAS  Google Scholar 

  25. S. Ogino, N. Nishida, R. Umemoto, M. Suzuki, M. Takeda, H. Terasawa, J. Kitayama, M. Matsumoto, H. Hayasaka, M. Miyasaka, and I. Shimada, Structure, 18, 649 (2010).

    Article  CAS  Google Scholar 

  26. S. Manju and K. Sreenivasan, J. Colloid Interface Sci., 359, 318 (2011).

    Article  CAS  Google Scholar 

  27. J. Klostergaard, E. Auzenne, S. C. Ghosh, M. Khodadadian, B. Rivera, D. Farquhar, R. E. Price, M. Ravoori, V. Kundra, and R. S. Freedman, Mol. Cancer Ther., 6, 3619S (2007).

    Google Scholar 

  28. H.-J. Cho, I.-S. Yoon, H. Y. Yoon, H. Koo, Y.-J. Jin, S.-H. Ko, J.-S. Shim, K. Kim, I. C. Kwon, and D.-D. Kim, Biomaterials, 33, 1190 (2012).

    Article  CAS  Google Scholar 

  29. T. Jiang, Z. Zhang, Y. Zhang, H. Lv, J. Zhou, C. Li, L. Hou, and Q. Zhang, Biomaterials, 33, 9246 (2012).

    Article  CAS  Google Scholar 

  30. R. Paliwal, S. R. Paliwal, G. P. Agrawal, and S. P. Vyas, Int. J. Pharm., 422, 179 (2012).

    Article  CAS  Google Scholar 

  31. W. Ke, Y. Zhao, R. Huang, C. Jiang, and Y. Pei, J. Pharm. Sci., 97, 2208 (2008).

    Article  CAS  Google Scholar 

  32. J. H. Hamman, Mar. Drugs, 8, 1305 (2010).

    Article  CAS  Google Scholar 

  33. B. Sarmento, A. Ribeiro, F. Veiga, P. Sampaio, R. Neufeld, and D. Ferreira, Pharm. Res., 24, 2198 (2007).

    Article  CAS  Google Scholar 

  34. H. Yoon and G. Kim, Macromol. Res., 20, 402 (2012).

    Article  CAS  Google Scholar 

  35. J. M. Smith, M. Dornish, and E. J. Wood, Biomaterials, 26, 3269 (2005).

    Article  CAS  Google Scholar 

  36. D. F. Evans, G. Pye, R. Bramley, A. G. Clark, T. J. Dyson, and J. D. Hardcastle, Gut, 29, 1035 (1988).

    Article  CAS  Google Scholar 

  37. C. Thouzeau, G. Peters, C. Le Bohec, and Y. Le Maho, J. Expe. Biol., 207, 2715 (2004).

    Article  CAS  Google Scholar 

  38. C. T. Tsao, C. H. Chang, Y. Y. Lin, M. F. Wu, J.-L. Wang, J. L. Han, and K. H. Hsieh, Carbohydr. Res., 345, 1774 (2010).

    Article  CAS  Google Scholar 

  39. C. Chun, S. M. Lee, S. Y. Kim, H. K. Yang, and S.-C. Song, Biomaterials, 30, 2349 (2009).

    Article  CAS  Google Scholar 

  40. X. Feng, Y.-J. Yuan, and J.-C. Wu, Bioorg. Med. Chem. Lett., 12, 3301 (2002).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, P. R. China

    Jiao Li, Pingsheng Huang, Longlong Chang, Xingwen Long, Anjie Dong & Liandong Deng

  2. Tianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, 300192, P. R. China

    Jinjian Liu, Liping Chu & Jianfeng Liu

  3. College of Pharmaceutical Science, Zhejiang University, Hangzhou, 310058, P. R. China

    Fuqiang Hu

Authors
  1. Jiao Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pingsheng Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Longlong Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xingwen Long
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Anjie Dong
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jinjian Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Liping Chu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Fuqiang Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jianfeng Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Liandong Deng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Jianfeng Liu or Liandong Deng.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, J., Huang, P., Chang, L. et al. Tumor targeting and pH-responsive polyelectrolyte complex nanoparticles based on hyaluronic acid-paclitaxel conjugates and Chitosan for oral delivery of paclitaxel. Macromol. Res. 21, 1331–1337 (2013). https://doi.org/10.1007/s13233-013-1171-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13233-013-1171-x

Keywords

Search

Navigation