Skip to main content
SpringerLink
Log in

Interaction of Doxorubicin and Dipalmitoylphosphatidylcholine Liposomes

  • Original Paper
  • Published:
Cell Biochemistry and Biophysics Aims and scope Submit manuscript

Abstract

The interaction between doxorubicin (DOX), an anthracycline antibiotic frequently used in chemotherapy, and zwitterionic dipalmitoylphosphatidylcholine (DPPC) was investigated using Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), and rheological measurements. FTIR results showed that DOX shifted the wavenumber of the PO2 − band for pure DPPC to a higher wavenumber. This may have been because of the strong interactions between the NH3 + group in DOX and the phosphate (PO2 −) group in the polar head of DPPC. The main transition temperature of DPPC liposomes was slightly shifted to a lower temperature for DPPC liposome-encapsulated DOX. This suggested that DOX had a significant effect on the acyl chains in the DPPC bilayers, and that its presence decreased the transition cooperativity of lipid acyl chains. There was also the appearance of an additional transition peak at nearly 136°C for the DPPC/DOX sample. These interactions between DOX and DPPC phospholipid would cause a decrease in the DPPC liposomes plastic viscosity and increase membrane fluidity. A better understanding of the interactions between DOX and lipid bilayers could help in the design and development of improved liposomal drug delivery systems.

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

Similar content being viewed by others

References

  1. Kawano, K., Takayama, K., Nagai, T., & Maitani, Y. (2003). Preparation and pharmacokinetics of pirarubicin loaded dehydration–rehydration vesicles. International Journal of Pharmaceutics, 252, 73–79.

    Article  PubMed  CAS  Google Scholar 

  2. Daemen, T., Regts, J., Meesters, M., Kate, M. T. T., Bakker-Woudenberg, I. A. J. M., & Scherphof, G. L. (1997). Toxicity of doxorubicin entrapped within long-circulating liposomes. Journal of Controlled Release, 44, 1–9.

    Article  CAS  Google Scholar 

  3. Shi, Y. Y., Zhao, H. M., & Wu, C. X. (1993). Relative binding free energy calculations of DNA to daunomycin and its 13-dihydro analogue. International Journal of Biological Macromolecules, 15, 247–251.

    Article  PubMed  CAS  Google Scholar 

  4. Rahman, A., Ganjei, A., & Neefe, J. R. (1986). Comparative immunotoxicity of free doxorubicin and doxorubicin encapsulated in cardiolipin liposomes. Cancer Chemotherapy and Pharmacology, 16, 28–34.

    PubMed  CAS  Google Scholar 

  5. Goormaghtigh, E., Huart, P., Brasseur, R., & Ruysschaert, J. M. (1986). Mechanism of inhibition of mitochondrial enzymatic complex I–III by adriamycin derivatives spectroscopy. Biochimica et Biophysica Acta, 861, 83–94.

    PubMed  CAS  Google Scholar 

  6. Joachim, K. S., Coats, E. A., Cordes, H. P., & Wiese, M. (1994). Drug membrane interaction and the importance for drug transport, distribution, accumulation, efficacy and resistance. Archiv der Pharmazie, 327, 601–610.

    Article  Google Scholar 

  7. Raimund, M., Kubinyi, H., & Folkers, G. (2002). Drug–membrane interactions. Germany: GmbH, Weinheim.

    Google Scholar 

  8. Zhao, L. Y., Feng, S. S., Kocherginsky, N., & Kostetski, I. (2007). DSC and EPR investigations on effects of cholesterol component on molecular interactions between paclitaxel and phospholipid within lipid bilayer membrane. International Journal of Pharmaceutics, 338, 258–266.

    Article  PubMed  CAS  Google Scholar 

  9. Constantinides, P. P., Inouchi, N., Tritton, T. R., Sartorelli, A. C., & Sturtevant, J. M. (1986). A scanning calorimetric study on the interaction of anthracyclines with neutral and acidic phospholipids alone and in binary mixtures. Journal of Biological Chemistry, 22, 10196–10203.

    Google Scholar 

  10. Barcelo, F., Escriba, P. V., & Miralles, F. (1990). A scanning calorimetric study of 345 natural and DNA antitumor anthracycline antibiotic–DNA complexes. Chemico-Biological Interaction, 74, 315–324.

    Article  CAS  Google Scholar 

  11. Seto, G. W. T., Marwaha, S., Kobewka, D. M., Lewis, R. N. A. H., Separovic, F., & McElhaney, R. N. (2007). Interactions of the Australian tree frog antimicrobial peptides aurein 1.2, citropin 1.1 and maculation 1.1 with lipid model membranes: Differential scanning calorimetric and Fourier transform infrared spectroscopic studies. Biochimica et Biophysica Acta, 1768, 2787–2800.

    Article  PubMed  CAS  Google Scholar 

  12. Toyran, N., & Severcan, F. (2007). Interaction between vitamin D2 and magnesium in liposomes: Differential scanning calorimetry and FTIR spectroscopy studies. Journal of Molecular Structure, 839, 19–27.

    Article  CAS  Google Scholar 

  13. Lewis, R. N. A. H., & McElhaney, R. N. (1996). FTIR spectroscopy in the study of hydrated lipids and lipid bilayer membranes. In H. H. Mantsch & D. Chapman (Eds.), Infrared spectroscopy of biomolecules (pp. 159–202). New York: Wiley.

    Google Scholar 

  14. Lewis, R. N. A. H., & McElhaney, R. N. (2002). Vibrational spectroscopy of lipids. In J. M. Chalmers & P. R. Griffith (Eds.), Handbook of vibrational spectroscopy (Vol. 5, pp. 3447–3464). Chichester: Wiley.

    Google Scholar 

  15. Rudra, A., Deepa, R. M., Ghosh, M. K., Ghosh, S., & Mukherjee, B. (2010). Doxorubicin-loaded phosphatidylethanolamine conjugated nanoliposomes: In vitro characterization and their accumulation in liver, kidneys, and lungs in rats. International Journal of Nanomedicine, 5, 811–823.

    PubMed  CAS  Google Scholar 

  16. Szoka, F., & Papahadjopoulos, D. (1978). Procedure for preparation of liposomes with large internal aqueous space and high capture by reverse-phase evaporation. Proceedings of the National Academy of Sciences of the United States of America, 75, 4194–4198.

    Article  PubMed  CAS  Google Scholar 

  17. Mayer, L. D., Tai, L. C., Bally, M. B., Mitilenes, G. N., Ginsberg, R. S., & Cullis, P. R. (1990). Characterization of liposomal systems containing doxorubicin entrapped in response pH gradients. Biochimica et Biophysica Acta, 1025, 143–151.

    Article  PubMed  CAS  Google Scholar 

  18. New, R. C. R. (1989). Liposomes: A practical approach (pp. 33–103). Oxford, UK: IRL Press.

    Google Scholar 

  19. Steffe, J. (1996). Rheological methods in food process engineering (2nd ed., p. 21). USA: Freeman Press, Mitchigan State University.

    Google Scholar 

  20. Mady, M. M., Darwish, M., Khalil, S., & Khalil, W. (2009). Biophysical studies on chitosan-coated liposomes. European Biophysics Journal, 38, 1127–1133.

    Article  PubMed  CAS  Google Scholar 

  21. Lefèvre, T., Toscani, S., Picquart, M., & Dugué, J. (2002). Crystallization of water in multilamellar vesicles. European Biophysics Journal, 31, 126–135.

    Article  PubMed  Google Scholar 

  22. Toyran, N., & Severcan, F. (2002). Infrared spectroscopic studies on the dipalmitoyl phosphatidylcholine bilayer interactions with calcium phosphate: Effect of vitamin D2. Spectroscopy, 16, 399–408.

    Article  CAS  Google Scholar 

  23. Mady, M. M., & Elshemey, W. (2011). Interaction of dipalmitoyl phosphatidylcholine (DPPC) liposomes and insulin. Molecular Physics, 109, 1593–1598.

    Article  CAS  Google Scholar 

  24. Mady, M. M., & Allam, M. A. (2012). The influence of low power microwave on the properties of DPPC vesicles. Physica Medica, 28, 48–53.

    Google Scholar 

  25. Mady, M. M., Fathy, M., Youssef, T., & Khalil, W. (2011). Biophysical characterization of gold nanoparticles-loaded liposomes. Physica Medica. doi:10.1016/j.ejmp.2011.10.001.

  26. Arrondo, J. L. R., Gofii, F. M., & Macarulla, J. M. (1984). Infrared spectroscopy of phosphatidylcholines in aqueous suspensions: A study of the phosphate group vibrations. Biochimica et Biophysica Acta, 794, 165–168.

    PubMed  CAS  Google Scholar 

  27. Stewart, L. C., & Kates, M. (1989). Intra-inter molecular hydrogen in diphytanylglycerol phospholipids an IR spectroscopic investigation. Biochemical Cell Biology, 68, 266–273.

    Article  Google Scholar 

  28. Kan-Zhi, L., Jackson, M., Sowa, M. G., Haisong, J., Dixon, I. M. C., & Mantsch, H. H. (1996). Modification of the extracellular matrix following myocardial infarction monitored by FTIR spectroscopy. Biochimica et Biophysica Acta, 1315, 73–77.

    Google Scholar 

  29. Cong, W., Liu, Q., Liang, Q., Wang, Y., & Luo, G. (2009). Investigation on the interactions between pirarubicin and phospholipids. Biophysical Chemistry, 143, 154–160.

    Article  PubMed  CAS  Google Scholar 

  30. Crowe, L., & Crowe, J. (1988). Trehalose and dry dipalmitoylphosphatidylcholine revisited. Biochimica et Biophysica Acta, 946, 193–201.

    Article  PubMed  CAS  Google Scholar 

  31. Ohtake, S., Schebor, C., Palecek, S., & de Pablo, J. J. (2004). Effect of sugar–phosphate mixtures on the stability of DPPC membranes in dehydrated systems. Cryobiology, 48, 81–89.

    Article  PubMed  CAS  Google Scholar 

  32. Heywang, C., Chazalet, M. S. P., Masson, M., & Bolard, J. (1996). Incorporation of exogenous molecules inside mono- and bilayers of phospholipids: Influence of the mode of preparation revealed by SERRS and surface pressure studies. Langmuir, 12, 6459–6467.

    Article  Google Scholar 

  33. Bernsdorff, C., Reszka, R., & Winter, R. (1999). Interaction of the anticancer agent Taxol (paclitaxel) with phospholipid bilayers. Journal of Biomedical Materials Research, 46, 141–149.

    Article  PubMed  CAS  Google Scholar 

  34. Fa, N., Ronkart, S., Schanck, A., Deleu, M., Gaigneaux, A., Goormaghtigh, E., et al. (2006). Effect of the antibiotic azithromycin on thermotropic behavior of DOPC or DPPC bilayers. Chemistry and Physics of Lipids, 144, 108–116.

    Article  PubMed  CAS  Google Scholar 

  35. Ladbrooke, B. D., Williams, R. M., & Chapman, D. (1968). Studies on lecithin–cholesterol–water interactions by differential scanning calorimetry and X-ray diffraction. Biochimica et Biophysica Acta, 150, 333–340.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Biophysics Department, Faculty of Science, Cairo University, 12613, Giza, Egypt

    Mohsen M. Mady

  2. Department of Physics and Astronomy, Faculty of Science, King Saud University, Riyadh, 11451, Saudi Arabia

    Mohsen M. Mady

  3. Physics Department, Faculty of Science, Helwan University, Cairo, Egypt

    Medhat W. Shafaa, Eman R. Abbase & Amine H. Fahium

  4. Medical Physics Department, Faculty of Medicine, Jazan University, Jazan, Saudi Arabia

    Medhat W. Shafaa

Authors
  1. Mohsen M. Mady
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Medhat W. Shafaa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eman R. Abbase
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Amine H. Fahium
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mohsen M. Mady.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mady, M.M., Shafaa, M.W., Abbase, E.R. et al. Interaction of Doxorubicin and Dipalmitoylphosphatidylcholine Liposomes. Cell Biochem Biophys 62, 481–486 (2012). https://doi.org/10.1007/s12013-011-9334-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12013-011-9334-x

Keywords

Search

Navigation