Skip to main content
SpringerLink
Log in

Separation of anticancer medicines carmustine, lomustine, semustine and melphalan by PAMAM dendrimer: a theoretical study

  • Original Paper
  • Published:
Journal of the Iranian Chemical Society Aims and scope Submit manuscript

Abstract

Much progress has been made in the treatment of cancer. However, it remains a significant challenge to treat as toxic chemotherapeutic drugs are often poorly tolerated when administered together, limiting the patient’s treatment options. A possible solution to this problem is anchoring drugs on the surface of nanoparticles. These systems have a variety of structures with sizes, shapes and materials which determine loading capacity, cellular targeting and stability. Dendrimers are a class of nanoparticles which have been investigated in this context. In this study, we investigated the functionalization of polyamidoamine (PAMAM) dendrimers with some anticancer medications that suppresses the growth of cancer cells (carmustine, lomustine, semustine and melphalan; 1–4). The possibility of drug release, drug delivery and drug separation by PAMAM was theoretically investigated and discussed. The predicted theoretical method will be interesting to remove the pollutants from the medical solutions by PAMAM dendrimer nanoclusters. The results of the modeling were obtained by MMFF94 and RHF/PM6 methods for all form of the PAMAM–medicines complexes. The obtained results by these two methods were shown same trend of the relative energy surfaces of the complexes of PAMAM–medicines 1–4.

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
Scheme 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

5. References

  1. S.H. Medina, M.E.H. EL-Sayed, Dendrimers as carriers for delivery of chemotherapeutic agents. Chem. Rev. 109, 3141–3157 (2009)

    Article  CAS  Google Scholar 

  2. B. Klajnert, M. Bryszewska, Dendrimers properties and applications. Acta Bio Chim. Pol. 48(1), 199–208 (2001)

    CAS  Google Scholar 

  3. B.K. Nanjwade, H.M. Bechra, G.K. Derkar, F.V. Manvi, V.K. Nanjwade, Dendrimers emerging polymers. For drug delivery system. Eur. J. Pharm. Sci. 38, 185–196 (2009)

    Article  CAS  Google Scholar 

  4. M.T. Morgan, Y. Nakanishi, Y. Kroll, D.J. Griset, A.P. Carnahan, M.A. Wathier, M. Oberlies, N.H. Manikumar, G. Wani, M.C. Grinstaff, Dendrimer-encapsulated camptothecins. Cancer Res. 66(24), 11913–11921 (2006)

    Article  CAS  Google Scholar 

  5. R.K. Tekade, T. Dutta, V. Gajbhiye, N.K. Jain, Exploring dendrimer towards dual drug delivery. J. Microencapsul. 26(4), 287–296 (2009)

    Article  CAS  Google Scholar 

  6. T. Dutta, Targeting potential and anti HIV activity of mannosylated fifth generation poly (propyleneimine) dendrimers. Biochim. Biophys. Acta 1770(4), 681–686 (2007)

    Article  CAS  Google Scholar 

  7. T. Dutta, M.J. Garg, Targeting of efavirenz loaded tuftsin conjugated poly(propyleneimine) dendrimers to HIV infected macrophages in vitro. Eur. J. Pharm. Sci. 34(2–3), 181–189 (2008)

    Article  CAS  Google Scholar 

  8. T. Dutta, H. Agashe, B. Garg, B. Minakshi, K. Prahlad, J.N. Madhulika, Poly (propyleneimine) dendrimer based nanocontainers for targeting of efavirenz to human monocytes/macrophages in vitro. J. Drug Target. 15(1), 84–96 (2007)

    Article  Google Scholar 

  9. C. Cheng, Y. Wu, Q. Li, Y. Xu, External electrostatic interaction versus internal encapsulation between cationic dendrimers and negatively charged drugs: which contributes more to solubility enhancement of the drugs? J. Phys. Chem. B 112(30), 8884–8890 (2008)

    Article  CAS  Google Scholar 

  10. P.A. Pizzo, D.G. Poplack, Principles and Practice of Pediatric Oncology, 5th edn. (Lippincott Williams & Wilkins, Philadelphia, 2006)

    Google Scholar 

  11. P.G. Corrie, G. Pippa, Cytotoxic chemotherapy: clinical aspects. Medicine 36(1), 24–28 (2008)

    Article  Google Scholar 

  12. B. Chabner, D.L. Longo, Cancer Chemotherapy and Biotherapy: Principles and Practice, 4th edn. (Lippincott Willians & Wilkins, Philadelphia, 2005)

    Google Scholar 

  13. G. Damia, M. D’Incalci, Mechanisms of resistance to alkylating agents. Cytotechnology 27(1–3), 165–173 (1998)

    Article  CAS  Google Scholar 

  14. F.P. Perera, Environment and cancer: who are susceptible? Science 278(5340), 1068–1073 (1997)

    Article  CAS  Google Scholar 

  15. X.C. He, Z.G. Qu, F. Xu, M. Lin, J.L. Wang, X.H. Shi, T.J. Lu, Molecular analysis of interactions between dendrimers and asymmetric membranes at different transport stages. Soft Matter 10, 139–148 (2014)

    Article  CAS  Google Scholar 

  16. X.C. He, M. Lin, T.J. Lu, Z.G. Qu, F. Xu, Molecular analysis of interactions between a PAMAM dendrimer–paclitaxel conjugate and a biomembrane. Phys. Chem. Chem. Phys. 17, 29507–29517 (2015)

    Article  CAS  Google Scholar 

  17. L. Canham, Nanosilicon for nanomedicine: a step towards biodegradable electronic implants? Nanomedicine (Lond) 8(10), 1573–1576 (2013)

    Article  CAS  Google Scholar 

  18. M.A. Horton, A. Khan, Medical nanotechnology in the UK: a perspective from the London centre for nanotechnology. Nanomedicine 2(1), 42–48 (2015)

    Article  Google Scholar 

  19. B.H. Schlegel, Ab initio molecular dynamics with born-oppenheimer and extended Lagrangian methods using atom centered basis functions. Bull. Kor. Chem. Chem. Soc. 24, 837–842 (2003)

    Article  CAS  Google Scholar 

  20. R. Chang, Physical Chemistry for the Biosciences (University Science Books, Sausalito, 2005)

    Google Scholar 

  21. E.G. Lewars, Computational Chemistry: Introduction to the Theory and Applications of Molecular and Quantum Mechanics (Springer, Berlin, 2010)

    Google Scholar 

  22. F. Ingrosso, B. Mennucci, J. Tomasi, Quantum mechanical calculations coupled with a dynamical continuum model for the description of dielectric relaxation: time dependent Stokes shift of coumarin C153 in polar solvents. J. Mol. Liq. 108, 21–46 (2003)

    Article  CAS  Google Scholar 

  23. Senn HM, Thiel W, QM/MM methods for biological systems. in Atomistic approaches in modern biology. ed: pp. 173–290, Springer, Berlin (2006)

  24. N. Jardillier, A. Goursot, One-electron quantum capping potential for hybrid QM/MM studies of silicate molecules and solids. Chem. Phys. Lett. 454, 65–69 (2008)

    Article  CAS  Google Scholar 

  25. D. Young, Computational chemistry: a practical guide for applying techniques to real world problems (John Wiley & Sons Inc, New York, 2004)

    Google Scholar 

  26. V.D. Khavryuchenko, O.V. Khavryuchenko, V.V. Lisnyak, High multiplicity states in disordered carbon systems: Ab initio and semiempirical study. Chem. Phys. 368, 83–86 (2010)

    Article  CAS  Google Scholar 

  27. Stewart JJP, Optimization of parameters for semiempirical methods V: Modification of NDDO approximations and application to 70 elements, J. Mol. Model. 13(12), 1173–1213 (2007). http://www.semichem.com/ampac/pm6.php. https://en.wikipedia.org/wiki/Semi-empirical_quantum_chemistry_method

  28. J.J.P. Stewart, Application of the PM6 method to modeling the solid state. J. Mol. Model. 14(6), 499–535 (2008)

    Article  CAS  Google Scholar 

  29. J.J.P. Stewart, Application of the PM6 method to modeling proteins. J. Mol. Mod. 15(7), 765–805 (2009)

    Article  CAS  Google Scholar 

  30. Spatran’10-Quantum Mechanics Program: (PC/x86)-1.1.0v4. 2011, Wavefunction Inc., USA

  31. P. Atkins, J. de Paula, Physical Chemistry, 8th edn. (Oxford University Press, New York, 2006)

    Google Scholar 

  32. R.G. Mortimer, Physical Chemistry, 3rd edn. (Elsevier Inc., USA, 2008)

    Google Scholar 

  33. Parimala K, Balachandran V, Vibrational spectroscopic (FTIR and FT Raman) studies, first order hyperpolarizabilities and HOMO, LUMO analysis of p-toluenesulfonyl isocyanate using ab initio HF and DFT methods, Spectrochim. Acta A Mol. Biomol. Spectros 81(1), 711–723 (2011). http://en.wikipedia.org/w/index.php? title = Mulliken_population_analysis&oldid = 572345005

  34. J.G. Bundy, A.W.J. Morriss, D.G. Durham, C.D. Campbell, G.I. Paton, Development of QSARs to investigate the bacterial toxicity and biotransformation potential of aromatic heterocylic compounds. Chemosphere 42, 885–892 (2001)

    Article  CAS  Google Scholar 

  35. A. Li, S.H. Yalkowsky, Predicting cosolvency. 1. Solubility ratio and solute logK ow. Ind. Eng. Chem. Res. 37, 4470–4475 (1998)

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physics, Science and Research Branch, Islamic Azad University, P. O. Box: 14665/678, Tehran, Iran

    Masoomeh Bayat & Seyed Mohammad Elahi

  2. Department of Organic Chemistry, Faculty of Chemistry, Razi University, P.O. Box: 67149- 67346, Kermanshah, Iran

    Avat Arman Taherpour

  3. Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Avat Arman Taherpour

  4. School of Chemistry, University of Melbourne, Melbourne, Australia

    Thomas Fellowes

  5. Bio21 Institute, University of Melbourne, Melbourne, Australia

    Thomas Fellowes

Authors
  1. Masoomeh Bayat
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Avat Arman Taherpour
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Seyed Mohammad Elahi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Thomas Fellowes
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Avat Arman Taherpour.

Ethics declarations

Conflict of interest

All authors declare that they have no conflict of interest.

Human and animal rights

This article does not contain any studies with human participants or animals performed by any of the authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bayat, M., Taherpour, A.A., Elahi, S.M. et al. Separation of anticancer medicines carmustine, lomustine, semustine and melphalan by PAMAM dendrimer: a theoretical study. J IRAN CHEM SOC 15, 1223–1234 (2018). https://doi.org/10.1007/s13738-018-1320-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13738-018-1320-4

Keywords

Search

Navigation