Skip to main content
SpringerLink
Log in

Synthesis and characterization of polyamidoamine conjugates of neridronic acid

  • Original Paper
  • Published:
Polymer Bulletin Aims and scope Submit manuscript

Abstract

Polyamidoamine conjugates of neridronic acid were synthesized by a one-pot aqueous phase Michael addition reaction of N, N′-methylenebisacrylamide with selected primary and secondary amines and neridronic acid. This reaction involved the use of water and it was performed at room temperature thereby making the reaction environmentally friendly and economically viable. These conjugates are potential prodrugs and they were characterized by nuclear magnetic resonance spectroscopy (NMR), Fourier transform spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscope (SEM) and energy-dispersive X-ray analysis (EDX). NMR, TGA, XRD and FTIR confirmed the successful incorporation of the bisphosphonate on to the carriers. The mass percentage incorporation of neridronic acid was found to be between 0.9 and 3.74 percent. 31P NMR exhibited the signal peak for the bisphosphonate at 19.0 ppm.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13
Fig. 14
Fig. 15
Fig. 16
Fig. 17
Fig. 18

Similar content being viewed by others

References

  1. Larson N, Ghandehari H (2012) Polymeric conjugates for drug delivery. Chem Mater 24:840–853

    Article  CAS  Google Scholar 

  2. Knop K, Hoogenboom R, Fischer D, Schubert US (2010) Poly(ethylene glycol) in drug delivery: pros and cons as well as potential alternatives. Angew Chem Int Ed 49:6288–6308

    Article  CAS  Google Scholar 

  3. Bentley MD, Harris JM, Kozlowski A (1999), “Heterobifunctional Poly(ethylene glycol) Derivatives and Methods for their preparation,” P.C.T. US99/23536

  4. Banerjee SS, Aher N, Patil R, Khandare J (2012), Review Article: Poly(ethylene glycol)-Prodrug Conjugates: Concept, Design, and Applications. J Drug Deliv, Volume 2012, Article ID 103973, 17 pages

  5. Agrawal RN, Joseph A, Mukerji A (2013) Polymeric prodrugs: recent achievements and general strategies. J Antivir Antiretrovir S15:12

    Google Scholar 

  6. Zhou Y, Cheng C, Yang S-T. Production of Malic Acid and Poly(l-malic acid) from Biomass Hydrolysates by Aureobasidium pullulans. http://www3.aiche.org/proceedings/content/Annual-2013/extended-abstracts/P343556.pdf. Accessed 09/04/2014

  7. Richardson S, Ferruti P, Duncan R (1999) Poly(amidoamine)s as Potential Endosomolytic Polymers: evaluation In Vitro and In Vivo Body Distribution in Normal and Tumour-Bearing Animals. J Drug Targeting 6:391–404

    Article  CAS  Google Scholar 

  8. Danusso F, Ferruti P (1970) Synthesis of Tertiary Amine Polymers. Polymer 11:88–113

    Article  CAS  Google Scholar 

  9. Ferruti P, Marchisio MA, Duncan R (2002) Poly(amidoamine)s: biomedical Applications. Macromol Rapid Commun 23:332–355

    Article  CAS  Google Scholar 

  10. Ferruti P, Ranucci E, Sartore L, Bignotti F, Marchisio MA, Bianciardi P, Veronese FM (1994) Recent Results on Functional Polymers and Macromonomers of Interest as Biomaterials or for Biomaterial Modification. Biomaterial 15:1235–1241

    Article  CAS  Google Scholar 

  11. N’Da DD, Neuse EW (2006) Polyamidoamines as Drug Carriers: synthesis of Polymers Featuring Extrachain-type Primary Amino Groups as Drug-anchoring Sites. S Afr J Chem 59:65–70

    Google Scholar 

  12. Caldwell G, Neuse EW, Stephanou A (1993) Synthesis of water-soluble polyimidoamines for biomedical application. II. Polymers possessing intrachain-type secondary amino groups suitable for side-chain attachment. J Appl Polym Sci 50:393–401

    Article  CAS  Google Scholar 

  13. Cavalli R, Bisazza A, Bussano R, Trotta M, Civra A, Lembo D, Ranucci E, Ferruti P (2011) Poly(amidoamine)–cholesterol conjugate nanoparticles obtained by electrospraying as novel tamoxifen delivery system. J Drug Deliv volume 2011, p 9

  14. Ferruti P, Ranucci E, Trotta F, Gianasi E, Evagorou EG, Wasil M, Wilson G, Duncan R (1999) Synthesis, characterisation and antitumour activity of platinum(II) complexes of novel functionalised poly(amido amine)s. Macromol Chem Phys 200:1644–1654

    Article  CAS  Google Scholar 

  15. Ranucci E, Suardi MA, Annunziata R, Ferruti P, Chiellini F, Bartoli C (2008) Poly(amidoamine) conjugates with disulfide-linked cholesterol pendants self-assembling into redox-sensitive nanoparticles. Biomacromol 9:2693–2704

    Article  CAS  Google Scholar 

  16. Davide G, Maurizio R, Ombretta V, Luca I, Silvano A (2013) Clinical development of neridronate: potential for new applications. Ther Clin Risk Manag 9:139–147

    Google Scholar 

  17. Quarta L, Corrado A, Melillo N, Trotta A, Scotto G, d’Onofrio F, Santoro N, Cantatore FP (2008) Combined effect of neridronate and specific antibiotic therapy in a case of tuberculous spondylodiscitis. Rheumatol Int 28:495–498

    Article  CAS  Google Scholar 

  18. Morabito N, Gaudio A, Lasco A, Catalano A, Atteritano M, Trifiletti A, Anastasi G, Melloni D, Frisina N (2004) Neridronate prevents bone loss in patients receiving androgen deprivation therapy for prostate cancer. J Bone Miner Res 19:1766–1770

    Article  CAS  Google Scholar 

  19. Gatti D, Viapiana O, Idolazzi L, Fracassi E, Adami S (2009) Neridronic acid for the treatment of bone metabolic diseases. Expert Opin Drug Metab Toxicol 5:1305–1311

    Article  CAS  Google Scholar 

  20. Van Beek ER, Lowik CWGM, Papapoulos SE (2002) Bisphosphonates suppress bone resorption by a direct effect on early osteoclast precursors without affecting the osteoclastogenic capacity of osteogenic cells: the role of protein geranylgeranylation in the action of nitrogen-containing bisphosphonates on osteoclast precursors. Bone 30:64–70

    Article  Google Scholar 

  21. Russell RG (2007) Bisphosphonates: mode of Action and Pharmacology. Paediatrics 119:S150

    Article  Google Scholar 

  22. Dunford JE (2010) molecular targets of the nitrogen containing bisphosphonates: the molecular pharmacology of prenyl synthase inhibition. Curr Pharm Des 16:2961

    Article  CAS  Google Scholar 

  23. General Side Effects of Bisphosphonates. http://cancerhelp.cancerresearchuk.org/about-cancer/treatment/bisphosphonate/general-side-effects-of-bisphosphonates. Accessed 11th October 2012

  24. Bisphosphonate Drugs—Side Effects of Bisphosphonate Drugs. http://www.algaecal.com/bisphosphonate-drugs-side-effects.html. Accessed 11th October 2012

  25. Barbucci R (2008) Amido-phosphonate or amido-bisphosphonate derivatives of carboxylated polysaccharides, preparation and biomedical uses thereof. Eur Patent Application, EP 1 994 945 A1

  26. Holmberg A (2011) Modified Hydroxypolymer Publication Classification Conjugates with Bone Seeking and Tumor Killing Moieties. US Patent Application Publication Pub No. US 2011/0118207 A1

  27. Miller K, Erez R, Segal E, Shabat D, Satchi-Fainaro R (2009) Targeting bone metastases with a bispecific anticancer and antiangiogenic polymer–alendronate–taxane conjugate. Angew Chem Int Ed 48:2949–2954

    Article  CAS  Google Scholar 

  28. Fresta M, Giammona G, Cavallaro G, Licciardi M, Paolino D (2012) Bisphosphonates–polyaspartamide conjugates as polymeric carrier for drug targeting to bones (From PATENTSCOPE database). World intellectual Property Organization, International Bureau. WO2012/098222 A1. http://patentscope.wipo.int/search/en/search.jsf

  29. Kieczykowski GR, Jobson RB, Melillo DG, Reinhold DF, Grenda VJ, Shinkai I (1995) Preparation of (4-amino-1-hydroxybutylidene) bisphosphonic acid sodium salt, MK-217 (alendronate sodium). An improved procedure for the preparation of 1-hydroxy-1, 1-bisphosphonic acids. J Org Chem 60:8310–8312

    Article  CAS  Google Scholar 

  30. Neuse EW (2008) Synthetic Polymers as Drug-Delivery Vehicles in Medicine, Metal-Based Drugs, Hindawi Publishing Corporation, Volume 2008, Article ID 469531, 19 pages. doi:10.1155/2008/469531

  31. Pasut G, Veronese FM (2007) Polymer–drug conjugation, recent achievements and general strategies. Prog Polym Sci 32:933–961

    Article  CAS  Google Scholar 

  32. Maeda H, Wu J, Sawa T, Matsumura Y, Hori K (2000) Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Control Release 65:271–284

    Article  CAS  Google Scholar 

  33. Ringsdorf H (1975) Structure and properties of pharmacologically active polymers. J Polym Sci Symp 51:135–153

    Article  CAS  Google Scholar 

  34. Miller PD (2005) Optimizing the management of postmenopausal osteoporosis with bisphosphonates: the emerging role of intermittent therapy. Clin Ther 27:361–376

    Article  CAS  Google Scholar 

  35. Tamami B, Fadavi A, Tamami M (2006) Polyacrylamide supported phenolate as a heterogeneous, efficient, recyclable, and selective catalyst for Aza- and thio-michael addition in aqueous media. Iran Polym J 15:799–807

    CAS  Google Scholar 

  36. da Silva FM, Jones J Jr (2001) Organic Reaction in Water. Part 3: Diastereoselectivity in Michael Additions of Thiophenol to Nitro Olefins in Aqueous Media. J. Braz. Chem. Soc. 12, no.2 São Paulo Mar./Apr

  37. Ferruti P, Bertoglio Riolo C, Soldi T, Pesavento M, Barbucci R, Beni MC, Casolaro M (1982) Applied macroinorganics. II. protonation and heavy metal ions complex-formation behavior of three crosslinked resins of poly(amido-amine) structure. J Appl Polym Sci 27:2239–2248

    Article  CAS  Google Scholar 

  38. Caldwell G, Neuse EW, Stephanou A (1993) Synthesis of water-soluble polyamidoamines for biomedical applications. 11. polymers possessing intrachain-type secondary amino groups suitable for side-chain attachment. J Appl Polym Sci 50:393–401

    Article  CAS  Google Scholar 

  39. Mulla SM, Phale PS, Saraf MR (2012) AdMet, Paper No.OM 006. www.metrologyindia.org/ebooks1/OM_006.pdf

Download references

Acknowledgments

The financial assistance of the National Research Foundation (NRF) towards this research is hereby acknowledged.

Author information

Authors and Affiliations

  1. Department of Chemistry, University of Fort Hare, Alice Campus, Eastern Cape, South Africa

    B. A. Aderibigbe

  2. Department of Chemical, Metallurgical and Material Engineering, Tshwane University of Technology, Pretoria, South Africa

    E. R. Sadiku, S. C. Agwuncha & S. J. Owonubi

  3. National Centre for Nano-structured Materials, CSIR, P. O. Box 395, Pretoria, 0001, South Africa

    S. Sinha Ray

  4. Department of Chemical Technology, University of Johannesburg, Johannesburg, South Africa

    S. Sinha Ray, X. Y. Mbianda & M. C. Fotsing

Authors
  1. B. A. Aderibigbe
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. R. Sadiku
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Sinha Ray
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. X. Y. Mbianda
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. C. Fotsing
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S. C. Agwuncha
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. S. J. Owonubi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to B. A. Aderibigbe.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Aderibigbe, B.A., Sadiku, E.R., Sinha Ray, S. et al. Synthesis and characterization of polyamidoamine conjugates of neridronic acid. Polym. Bull. 72, 417–439 (2015). https://doi.org/10.1007/s00289-014-1286-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00289-014-1286-z

Keywords

Search

Navigation