Skip to main content
SpringerLink
Log in

Water-Soluble Macromolecular Platinum Conjugates Derived from 1,2-Dihydroxyl-Functionalized Carrier Polymers

  • Published:
Journal of Inorganic and Organometallic Polymers and Materials Aims and scope Submit manuscript

Abstract

The class of platinum-containing bioactive agents, including cisplatin as the prototype, and structurally related second- and third-generation compounds, has developed during the past two decades as one of the most important family of antitumor drugs. However, despite a highly valued general antineoplastic performance profile, their unrestricted oncological administration continues to be hampered by pharmacological shortcomings, notably excessive toxicity and induction of drug resistance. This has prompted ongoing intensive development activities in pharmaceutic laboratories worldwide, and one of the most promising approaches emanating from these activities involves the drug conjugation to biomedically functional, water-soluble carrier polymers. Such macromolecular conjugates, judiciously designed and synthesized, provide significant pharmacological advantages over non-polymeric drug systems, notably increased cell specificity and facilitated cell entry, paired with reduced toxicity and resistance problems. In the present project, this technology has been applied specifically to the synthesis of Pt-containing polymers in which the metal is carrier-bound via dihydroxylatoplatinum chelation. In the cancerous target cell, such conjugates will deliver the free bioactive Pt complex hydrolytically for its cytotoxic action. The water-soluble polymeric products, fractionated by dialysis in membrane tubing with molecular-mass cut-off of 25,000, will be submitted to an outside institution for in vitro evaluation of cytotoxic properties.

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

Scheme 1
Scheme 2
Scheme 3
Scheme 4
Scheme 5
Scheme 6
Scheme 7
Scheme 8
Scheme 9
Scheme 10
Scheme 11
Scheme 12

Similar content being viewed by others

References

  1. A. Prestayko, S. Crooke, S. Carter (eds.) Cisplatin: Current Status and New Developments (Academic Press, New York, 1980)

  2. N. Farrell, Transition Metal Complexes as Drugs and Chemotherapeutic Agents (Kluwer Academic, Dordrecht, 1987), p.67

  3. W.R. Waud, Cancer Chemotherapeutic Agents, ed. by W.D. Foye (Amer. Chem. Soc. Washington, DC, 1995), p. 121

  4. E.W. Neuse, S. Afr. J. Sci. 95, 509 (1999)

    CAS  Google Scholar 

  5. M.J. McKeage, Expert Opin. Investig. Drugs. 14, 1033 (2005)

    Article  CAS  Google Scholar 

  6. D.W. Siegmann-Louda, C.E. Carraher, Jr., Macromolecules Containing Metal and Metal-like Elements, chap. 6, vol. 3, ed by A. S. Abd-El-Aziz et al. (Wiley, New York, 2004)

  7. M. Galanski, B.K. Keppler, Anti-Cancer Agents Med. Chem. 7, 55 (2007)

    Article  CAS  Google Scholar 

  8. R. Duncan, Nat. Rev. Drug Discov. 2, 247 (2003)

    Article  Google Scholar 

  9. J. Kopeček, Eur. J. Pharm. Sci. 20, 1 (2003)

    Article  Google Scholar 

  10. R.J. Christie, D.W. Grainger, Adv. Drug Deliv. Rev. 55, 421 (2003)

    Article  CAS  Google Scholar 

  11. R. Duncan, M.J. Vicent, F. Grego, R.W. Nicholson, Endocr. Relat. Cancer 12, S189 (2005)

    Article  CAS  Google Scholar 

  12. A. Nori, J. Kopeček, Adv. Drug Deliv. Rev. 57, 609 (2005)

    Article  CAS  Google Scholar 

  13. E.W. Neuse, in Macromolecules Containing Metal and Metal-like Elements, vol. 3, ed. by A.S. Abd-El-Aziz, C.E. Carraher, et al. (Wiley, New York, 2004), p. 89

    Chapter  Google Scholar 

  14. H. Maeda, Adv. Drug Deliv. Rev. 6, 181 (1991)

    Article  CAS  Google Scholar 

  15. J. Bariyanga, M.T. Johnson, E.M. Mmutlane, E.W. Neuse, J. Inorg. Organometal. Polym. Mater. 15, 335 (2005)

    Article  CAS  Google Scholar 

  16. L.L. Komane, E.H. Mukaya, E.W. Neuse, J. Inorg. Organometal. Polym. Mater. 18, 111 (2008)

    Article  CAS  Google Scholar 

  17. T. Smit, J.R. Snyman, E.W. Neuse, L. Bohm, C.E.J. van Rensburg, Anti-Cancer Drugs 16, 1 (2005)

    Article  Google Scholar 

  18. M.G. Meirim, E.W. Neuse, G.C. Caldwell, J. Appl. Polym. Sci. 73, 2143 (1999)

    Article  CAS  Google Scholar 

  19. F. Danusso, P. Ferruti, Polymer 11, 88 (1970)

    Article  CAS  Google Scholar 

  20. P. Ferruti, M.A. Marchisio, R. Duncan, Macromol. Rapid Commun. 23, 332 (2002)

    Article  CAS  Google Scholar 

  21. G. Caldwell, E.W. Neuse, S. Afr. J. Chem. 45, 93 (1992)

    CAS  Google Scholar 

  22. G. Caldwell, E.W. Neuse, A. Stephanou, J. Appl. Polym. Sci. 50, 393 (1993)

    Article  CAS  Google Scholar 

  23. M.G. Meirim, E.W. Neuse, G. Caldwell, J. Inorg. Organometal. Polym. 8, 225 (1998)

    Article  CAS  Google Scholar 

  24. P. Neri, G. Antoni, F. Benvenuti, F. Cocola, G. Gazzai, J. Med. Chem. 16, 893 (1973)

    Article  CAS  Google Scholar 

  25. P. Neri, G. Antoni, Macromol. Synt. 8, 25 (1982)

    CAS  Google Scholar 

  26. G. Caldwell, E.W. Neuse, G. Perlwitz, J. Appl. Polym. Sci. 66, 911 (1997)

    Article  CAS  Google Scholar 

  27. D.D. N’Da, E.W. Neuse, M. Nell, C.E.J. van Rensburg, S. Afr. J. Chem. 59, 33 (2003)

    Google Scholar 

  28. J.D. Hoeschele, N. Farrell, W.R. Turner, C.D. Rithner, Inorg. Chem. 27, 4106 (1988)

    Article  CAS  Google Scholar 

  29. M.L. de Machado, E.W. Neuse, A.G. Perlwitz, S. Schmitt, Polym. Adv. Technol. 1, 275 (1990)

    Article  Google Scholar 

  30. J. Drobnik, V. Saudek, J. Vlasak, J. Kalal, J. Polym. Sci. Polym. Symp. 66, 65 (1979)

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors gratefully acknowledge grants from the South African Medical Research Council, the National Research Foundation, and the Western Platinum Refinery. Generous solvent donations were made by Sasol Ltd., Engen Chemicals, and Bayer (Pty) Ltd. Special thanks are due also to Mr. Jan de Bruin, Anglo-American Research Laboratories, for performing the microanalytical platinum determinations.

Author information

Authors and Affiliations

  1. School of Chemistry, University of the Witwatersrand, Private Bag 3, Wits, 2050, South Africa

    David D. N’Da & Eberhard W. Neuse

Authors
  1. David D. N’Da
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eberhard W. Neuse
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eberhard W. Neuse.

Additional information

The authors wish to dedicate this study to Dr. Charles U. Pittman, Jr. in recognition of his contributions to the field of inorganic and organometallic polymers.

Rights and permissions

Reprints and permissions

About this article

Cite this article

N’Da, D.D., Neuse, E.W. Water-Soluble Macromolecular Platinum Conjugates Derived from 1,2-Dihydroxyl-Functionalized Carrier Polymers. J Inorg Organomet Polym 20, 468–477 (2010). https://doi.org/10.1007/s10904-010-9326-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10904-010-9326-0

Keywords

Search

Navigation