Skip to main content
SpringerLink
Log in

Synthesis and characterization of polyester-based dendrimers containing peripheral arginine or mixed amino acids as potential vectors for gene and drug delivery

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

Abstract

Macromolecular systems with well-defined sizes, shapes and high controlled architecture like dendrimers are of eminent interest in nanomedical applications such as drug delivery, gene transfection, and imaging. In this paper versatile protocols for the synthesis of polyester-based, hydrolysable, polycationic dendrimers have been setup. Fourth and fifth generation dendrimers equipped with several peripheral hydroxyl groups were prepared from 2, 2-bis(hydroxymethyl)propanoic acid. They were successfully esterified with arginine alone or mixed with lysine or O-methyltyrosine and with dipeptide arginine-glycine and seven polycationic dendrimers were finally obtained as hydrochlorides. Their structures and composition were confirmed by NMR analysis and by experimental molecular weight computed by volumetric titration and their buffer capacity was higher than fourth generation polyamidoamine (G4- PAMAM) derivatives taken as reference. The synthesized dendrimers harmonize a polycationic character and a buffer capacity which presuppose a good transfection efficiency with a degradable scaffold thus appearing as a promising team of new non-toxic vectors for biomedical applications.

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. R. Hourani and A. Kakkar, Macromol. Rapid Commun., 31, 947 (2010).

    Article  CAS  Google Scholar 

  2. M. Sowinska and Z. Urbanczyk-Lipkowska, New J. Chem., 38, 2168 (2014).

    Article  CAS  Google Scholar 

  3. P. Kesharwani, K. Jain, and N. Jain, Progr. Polym. Sci., 39, 268 (2014).

    Article  CAS  Google Scholar 

  4. J. Datija, V. V. R. Sai, and S. Mukherji, S. J. Mater. Chem., 21, 14367 (2011).

    Article  Google Scholar 

  5. A.-M. Caminade, in Dendrimers: Towards Catalytic, Material and Biomedical Uses, A-M. Caminade, C-O. Turrin, R. Laurent, A. Ouali, and B. Delavaux-Nicot, Eds., John Wiley & Sons Ltd, Chichester, UK., 2011, Ch. 15, pp 375–392.

  6. J.-H. Kim, K. Park, H. Y. Nam, S. Lee, K. Kim, and I. C. Kwon, Progr. Polym. Sci., 32, 1031 (2007).

    Article  CAS  Google Scholar 

  7. Z. Wang, G. Niu, and X. Chen, Pharm. Res., 31, 1358 (2014).

    Article  CAS  Google Scholar 

  8. C. Dufès, I. F. Uchegbu, and A. G. Schätzlein, Adv. Drug Deliv. Rev., 57, 2177 (2005).

    Article  Google Scholar 

  9. H. Eliyahu, Y. Barenholz, and A. Domb, Molecules, 10, 34 (2005).

    Article  CAS  Google Scholar 

  10. D. W. Pack, A. S. Hoffman, S. Pun, and P. S. Stayton, Nat. Rev. Drug Disc., 4, 581 (2005).

    Article  CAS  Google Scholar 

  11. D. Schaffert and E. Wagner, Gene Ther., 15, 1131 (2008).

    Article  CAS  Google Scholar 

  12. M. A. Mintzer and E. E. Simanek, Chem. Rev., 109, 259 (2009).

    Article  CAS  Google Scholar 

  13. S. O’Rorke, M. Keeney, and A. Pandit, Progr. Polym. Sci., 35, 441 (2010).

    Article  Google Scholar 

  14. H._M. Marvaniya, P. K: Parikh, V. R. Patel, K. N. Modi, and D. J. Sen, J. Chem. Pharm. Res., 2, 97 (2010).

    CAS  Google Scholar 

  15. X. Guo and L. Huang, Acc. Chem. Res., 45, 971 (2012).

    Article  CAS  Google Scholar 

  16. Y. Yue and C. Wu, Biomater. Sci., 1, 152 (2013).

    Article  CAS  Google Scholar 

  17. S. Biswas and V. P. Torchilin, Pharmaceuticals, 6, 161 (2013).

    Article  CAS  Google Scholar 

  18. N. Taghavi Pourianazar, P. Mutulu, and U. Gunduz, J. Nanopart. Res., 16, 2342/1 (2014).

    Article  Google Scholar 

  19. G. R. Newkome, and C. D. Shreiner, Polymer, 49, 1 (2008).

    Article  CAS  Google Scholar 

  20. J. D. Eichman, A. S. U. Bielinska, J. F. Kukowska-Latallo, and J. R. Baker Jr., Sci. Technol. Today, 3, 232 (2000).

    Article  CAS  Google Scholar 

  21. H. Zong, D. Shah, K. Selwa, R. E. Tsuchida, R. Rattan, J. Mohan, A. B. Stein, J. B. Otis, and S. N. Goonewardena, Chem. Open, 4, 335 (2015).

    CAS  Google Scholar 

  22. L. Han, R. Huang, S. Liu, S. Huang, and C. Jiang, Mol. Pharm., 7, 2156 (2010).

    Article  CAS  Google Scholar 

  23. Y. Gao, Z. Li, X. Xie, C. Wnaga, J. You, F. Moa, B. Jin, J. Chen, J. Shao, H. Chen, and L. Jia, Eur. J. Pharm. Sci., 70, 55 (2015).

    Article  CAS  Google Scholar 

  24. Y. Zhang, T. P. Thomas, K-H. Lee, M. Li, H. Zong, A. M. Desai, A. Kotlyar, B. Huang, H. M. M. Banaszak, and J. R. Baker Jr., Bioorg. Med. Chem., 19, 2557 (2011).

    Article  CAS  Google Scholar 

  25. S. L. Mekuria, T. A. Debele, H-Y. Chou, and H-C. Tsai, J. Phys. Chem. B, 120, 123 (2016).

    Article  CAS  Google Scholar 

  26. R. B. Kolhatkar, K. M. Kitchens, P. W. Swaan, and H. Ghandehari, Bioconj. Chem., 18, 2054 (2007).

    Article  CAS  Google Scholar 

  27. C. L. Waite, S. M. Sparks, K. E. Uhrich, and C. M. Roth, BMC Biotechnol., 9, 9 (2009).

    Article  Google Scholar 

  28. L. Jianfeng, L. Jinjian, C. Liping, T. Lingling, G. Hongjun, Y. Cuihong, W. Dezhi, S. Linqi, K. Deling, and L. Zongjin, J. Nanosci. Nanotechnol., 14, 3305 (2014).

    Article  Google Scholar 

  29. M. Ciolkowski, J. F. Petersen, M. Ficker, A. Janaszewska, J. B. Christensen, B. Klajnert, and M. Bryszewska, Nanomed-Nanotechnol., 8, 815 (2012).

    Article  CAS  Google Scholar 

  30. A. Ghilardi, D. Pezzoli, M. C. Bellucci, C. Malloggi, A. Negri, A. Sgnappa, G. Tedeschi, G. Candiani, and A. Volonterio, Bioconjug. Chem., 24, 1928 (2013).

    Article  CAS  Google Scholar 

  31. H. Arima, K. Motoyama, and T. Higashi, Adv. Drug Deliv. Rev., 65, 1204 (2013).

    Article  CAS  Google Scholar 

  32. R. S. Navath, A. R. Menjoge, B. Wang, R. Romero, S. Kannan, and R. M. Kannan, Biomacromolecules, 11, 1544 (2010).

    Article  CAS  Google Scholar 

  33. J. H. Park, J-S. Park, and J. S. Choi, Macromol. Res., 22, 500 (2014).

    Article  CAS  Google Scholar 

  34. F. Wang, Y. Wang, H. Wang, N. Shao, Y. Chen, and Y. Cheng, Biomaterials, 35, 9187 (2014).

    Article  CAS  Google Scholar 

  35. S. J. Lam, A. Sulistio, K. Ladewig, E. H. H. Wong, A. Blencowe, and G. G. Qiao, Austr. J. Chem., 67, 592 (2014).

    Article  CAS  Google Scholar 

  36. H. Y. Nam, K. Nam, H. J. Hahn, B. H. Kim, H. J. Lim, H. J. Kim, J. S. Choi, and J. S. Park, Biomaterials, 30, 665 (2009).

    Article  CAS  Google Scholar 

  37. M. Liu, J. Chen, Y-N. Xue, W-M. Liu, R-X. Zhuo, and S-W. Huang, Bioconjug. Chem., 20, 2317 (2009).

    Article  Google Scholar 

  38. Q. A. A. Eltoukhy, D. J. Siegwart, C. A. Alabi, J. S. Rajan, R. Langer, and D. G. Anderson, Biomaterials, 33, 3594 (2012).

    Article  CAS  Google Scholar 

  39. C. J. Bishop, T-M. Ketola, S. Y. Tzeng, J. C. Sunshine, A. Urttio, H. Lemmetyinen, E. Vuorimaa-Laukkanen, M. Yliperttula, and J. J. Green, J. Am. Chem. Soc., 135, 6951 (2013).

    Article  CAS  Google Scholar 

  40. K. L. Chang, Y. Higuchi, S. Kawakami, F. Yamashita, and M. Hashida, J. Control. Release, 156, 195 (2011).

    Article  CAS  Google Scholar 

  41. Y. Wen, Z. Guo, Z. Du, R. Fang, H. Wu, X. Zeng, C. Wang, M. Feng, and S. Pan, Biomaterials, 33, 8111 (2012).

    Article  CAS  Google Scholar 

  42. F. Wang, Y. Wang, H. Wang, N. Shao, Y. Chen, and Y. Cheng, Biomaterials, 35, 9187 (2014).

    Article  CAS  Google Scholar 

  43. J. Shi, J. G. Schellinger, R. N. Johnson, J. L. Choi, B. Chou, E. L. Anghel, and S. H. Pun, Biomacromolecules, 14, 1961 (2013).

    Article  CAS  Google Scholar 

  44. I. Nakase, H. Akita, K. Kogure, A. Gräslund, Ü. Langel, H. Harashima, and S. Futaki, Acc. Chem. Res., 45, 1132 (2012).

    Article  CAS  Google Scholar 

  45. I. Nakase, G. Tanaka, and S. Futaki, Mol. Bio Syst., 9, 855 (2013).

    CAS  Google Scholar 

  46. C. Liu, X. Liu, P. Rocchi, F. Qu, J. L. Iovanna, and L. Peng, Bioconjug. Chem., 25, 521 (2014).

    Article  CAS  Google Scholar 

  47. X. Liu, C. Liu, J. Zhou, C. Chen, F. Qu, J. J. Rossi, P. Rocchi, and L. Peng, Nanoscale, 7, 3867 (2015).

    Article  CAS  Google Scholar 

  48. J. B. Kim, J. S. Choi, K. Nam, M. Lee, J. S. Park, and J. K. Lee, J. Control. Release, 114, 110 (2006).

    Article  CAS  Google Scholar 

  49. T. Kim, C. Z. Bai, K. Nam, and J. Park, J. Control. Release, 136, 132 (2009).

    Article  CAS  Google Scholar 

  50. Q. Peng, J. Zhu, Y. Yu, L. Hoffman, and X. Yang, J. Biomater. Sci. Polym. Ed., 26, 1163 (2015).

    Article  CAS  Google Scholar 

  51. A. Carlmark, E. Malstrӧm, and M. Malkoch, Chem. Soc. Rev., 42, 5858 (2013).

    Article  CAS  Google Scholar 

  52. N. Feliu, M. V. Walter, M. I. Montañez, A. Kunzmann, A. Hult, A. Nyström, M. Malkoch, and B. Fadeel, Biomaterials, 33, 1970 (2012).

    Article  CAS  Google Scholar 

  53. J. S. Moore and S. I. Stupp, Macromolecules, 23, 65 (1990).

    Article  CAS  Google Scholar 

  54. H. Ihre, A. Hult, J. M. J Fréchet, and I. Gitsov, Macromolecules, 31, 4061 (1998).

    Article  CAS  Google Scholar 

  55. M. Zhao, J. Liu, X. Zhang, L. Peng, C. Li, and S. Peng, Bioorg. Med. Chem., 17, 3680 (2009).

    Article  CAS  Google Scholar 

  56. A. I. Vogel, in Elementary Practical Organic Chemistry. Part III. Quantitative Organic Analysis, Longman Ed., 1st ed., London, 1958, Ch. 20, p 702.

    Google Scholar 

  57. F. Von Seel, in Grundlagen der Analytischen Chemie, G. Geier, Ed., 5th ed., Verlag Chemie, Weinheim, 1970, Vol. 82, p 962.

    Google Scholar 

  58. L. Aravindana, K. A. Bicknell, G. Brooks, V. V. Khutoryanskiya, and A. C. Williams, Int. J. Pharm., 378, 201 (2009).

    Article  Google Scholar 

  59. J. M. Benns, J. S. Choi, R. I. Mahato, J. S. Park, and S. W. Kim, Bioconjug. Chem., 11, 637 (2000).

    Article  CAS  Google Scholar 

  60. J. Yang, Q. Zhang, H. Chang, and Y. Cheng, Chem. Rev., 115, 5274 (2015).

    Article  CAS  Google Scholar 

  61. H. Kessler and M. Molter, J. Am. Chem. Soc., 98, 5969 (1976).

    Article  CAS  Google Scholar 

  62. S. Y. Gwang, M. B. Yun, C. Hye, K. Bokyung, S. C. Insung, and S. C. Joon, Bioconjug. Chem., 22, 1046 (2011).

    Article  Google Scholar 

  63. N. Heigl, S. Bachmann, C. H. Petter, M. Marchetti-Deschmann, G. Allmaier, G. K. Bonn, and C. W. Huck, Anal. Chem., 81, 5655 (2009).

    Article  CAS  Google Scholar 

  64. Y. Zeng, Y. Kurokawa, T. T. Win-Shwe, Q. Zeng, S. Hirano, Z. Zhang, and H. Sone, J. Toxicol. Sci., 41, 351 (2016).

    Article  CAS  Google Scholar 

Download references

Author information

Author notes

  1. These authors equally contributed to this work.

Authors and Affiliations

  1. Dipartimento di Farmacia, Sezione di Chimica e Tecnologie Farmaceutiche e Alimentari, Università di Genova, Viale Cembrano 4, I-16148, Genova, Italy

    Silvana Alfei & Sara Castellaro

Authors
  1. Silvana Alfei
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sara Castellaro
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Silvana Alfei.

Additional information

Acknowledgments: This work has been supported by University of Genoa (Progetti di Ateneo). The authors are very thankful to Dr Gaby Brice Taptue for language help and to Mr Gagliardo Osvaldo for Elemental analysis.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Alfei, S., Castellaro, S. Synthesis and characterization of polyester-based dendrimers containing peripheral arginine or mixed amino acids as potential vectors for gene and drug delivery. Macromol. Res. 25, 1172–1186 (2017). https://doi.org/10.1007/s13233-017-5160-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13233-017-5160-3

Keywords

Search

Navigation