Advertisement

Evaluation of the physicochemical properties of liposomes as potential carriers of anticancer drugs: spectroscopic study

  • Danuta PentakEmail author
Research Paper

Abstract

Vesicle size and composition are a critical parameter for determining the circulation half-life of liposomes. Size influences the degree of drug encapsulation in liposomes. The geometry, size, and properties of liposomes in an aqueous environment have to be described to enable potential applications of liposome systems as drug carriers. The characteristics of multiple thermotropic phase transitions are also an important consideration in liposomes used for analytical and bioanalytical purposes. The aim of this study was to evaluate the physicochemical properties of liposomes which accommodate hydrophilic and amphiphilic drugs used in cancer therapy. The studied liposomes were prepared with the involvement of the modified reverse-phase evaporation method (mREV). The prepared liposomes had a diameter of 70–150 nm. The analyzed compounds were 1-β-d-arabinofuranosylcytosine, cyclophosphamide, and ifosfamide. In literature, there is no information about simultaneous incorporation of cytarabine, ifosfamide, and cyclophosphamide, in spite of the fact that these drugs have been used for more than 30 years. A combination of the examined drugs is used in CODOX-M/IVAC therapy. CODOX-M/IVAC (cyclophosphamide, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine) is one of the currently preferred intensive-dose chemotherapy regimens for Burkitt lymphoma (BL). The present research demonstrates the pioneering studies of incorporation of ifosfamide into liposome vesicles, location of and competition between the analyzed drugs and liposome vesicles. The applied methods were nuclear magnetic resonance (NMR), atomic force microscopy (AFM), differential scanning calorimetry (DSC).

Graphical Abstract

Keywords

Nanomedicine Drug delivery Liposome mREV NMR AFM DSC 

Notes

Acknowledgments

This study was supported by the State Committee for Scientific Research in Poland (N N204 139039).

Supplementary material

11051_2016_3427_MOESM1_ESM.doc (66 kb)
Supplementary material 1 (DOC 66 kb)

References

  1. Albrecht TR, Grutter P, Horne D, Rugard D (1991) Frequency modulation detection using high-Q cantilevers for enhanced force microscope sensitivity. J Appl Phys 69:668–673CrossRefGoogle Scholar
  2. Allen TM, Cullis PR (2013) Liposomal drug delivery systems: from concept to clinical applications. Adv Drug Deliv Rev 65:36–48CrossRefGoogle Scholar
  3. Andresen TL, Jensen SS (2005) Advanced strategies in liposomal cancer therapy: problems and prospects of active and tumor specific drug release. Prog Lipid Res 44:68–97CrossRefGoogle Scholar
  4. Bray F, Jemal A, Forman D (2012) Global cancer transitions according to the Human Development Index (2008–2030): a population-based study. Lancet Oncol 13:790–801CrossRefGoogle Scholar
  5. Chauhan VP, Stylianopoulos T, Boucher Y, Jain RK (2011) Delivery of molecular and nanoscale medicine to tumors: transport barriers and strategies. Annu Rev Chem Biomol Eng 2:281–298CrossRefGoogle Scholar
  6. Fernandez-Fernandez A, Manchanda R, McGoron AJ (2011) Theranostic applications of nanomaterials in cancer: drug delivery, image-guided therapy, and multifunctional platforms. Appl Biochem Biotechnol 165:1628–1651CrossRefGoogle Scholar
  7. Gabizon AA, Shmeeda H, Zalipsky S (2006) Pros and cons of the liposome platform in cancer drug targeting. J Liposome Res 16:175–183CrossRefGoogle Scholar
  8. Gaynor ER, Ultmann JE, Golomb HM, Sweet DL (1985) Treatment of diffuse histiocytic lymphoma (DHL) with COMLA (cyclophosphamide, oncovin, methotrexate, leucovorin, cytosine arabinoside): a 10-year experience in a single institution. J Clin Oncol 3:1596–1604Google Scholar
  9. Gregoriadis G (1974) Drug entrapment in liposomes; possibilities for chemotherapy. Biochem Soc Trans 2:117–119CrossRefGoogle Scholar
  10. Guglielmi C, Amadori S, Martelli M (1992) F-MACHOP in advanced aggressive lymphoma. Leuk Lymphoma 7:205–209Google Scholar
  11. Jain RK, Stylianopoulos T (2010) Delivering nanomedicine to solid tumors. Nat Rev Clin Oncol 7:653–664CrossRefGoogle Scholar
  12. Kaye SB, Richardson VJ (1979) Potential of liposomes as drug-carriers in cancer chemotherapy: a review. Cancer Chemother Pharmacol 3:81–85CrossRefGoogle Scholar
  13. Leonenko ZV, Carnini A (2000) Supported planar bilayer formation by vesicle fusion: the interaction of phospholipid vesicles with surfaces and the effect of gramicidin on bilayer properties using atomic force microscopy. Biochim Biophys Acta Biomembr 1509:131–147CrossRefGoogle Scholar
  14. Liang X, Mao G (2004) Probing small unilamellar eggPC vesicles on mica surface by atomic force microscopy. Colloids Surf B Biointerfaces 34:42–51CrossRefGoogle Scholar
  15. Malam Y, Loizidou M, Seifalian AM (2009) Liposomes and nanoparticles: nanosized vehicles for drug delivery in cancer. Trends Pharmacol Sci 30:592–599CrossRefGoogle Scholar
  16. Mead GM, Sydes MR, Walewski J, Grigg A, Hatton CS, Norbert P, Guarnaccia C, Lewis MS, McKendrick J, Stenning SP, Wright D (2002) An international evaluation of CODOX-M and CODOX-M alternating with IVAC in adult Burkitt’s lymphoma:results of United Kingdom Lymphoma Group LY06 study. Ann Oncol 13:1264–1274CrossRefGoogle Scholar
  17. Merisko-Liversidge EM, Liversidge GG (2008) Drug nanoparticles: formulating poorly water-soluble compounds. Toxicol Pathol 36:43–48CrossRefGoogle Scholar
  18. Park YS (2002) Tumor-directed targeting of liposomes. Biosci Rep 22:267–281CrossRefGoogle Scholar
  19. Parker BA, Santarelli M (1993) AMOPLACE treatment of intermediate-grade and high-grade malignant lymphoma: a cancer and leukemia Group B study. J Clin Oncol 11:248–254Google Scholar
  20. Pentak D (2014) Physicochemical properties of liposomes as potential anticancer drugs carriers. Interaction of etoposide and cytarabine with the membrane: spectroscopic studies. Spectrochim Acta A Mol Biomol Spectrosc 122:451–460CrossRefGoogle Scholar
  21. Pentak D, Sułkowska A, Sułkowski WW (2008) Application of NMR and UV spectroscopy in the study of interactions between anticancer drugs and their phospholipide carriers. J Mol Struct 887:187–193CrossRefGoogle Scholar
  22. Rastogia R, Ananda S, Koula V (2009) Flexible polymerosomes—an alternative vehicle for topical delivery. Colloids Surf B 72:161–166CrossRefGoogle Scholar
  23. Rodrigues C, Gameiro P (2003) Interaction of rifampicin and isoniazid with large unilamellar liposomes: spectroscopic location studies. Biochim Biophys Acta 1620:151–159CrossRefGoogle Scholar
  24. Ruozi B, Tosi G, Forni F (2005) Atomic force microscopy and photon correlation spectroscopy: two techniques for rapid characterization of liposomes. Eur J Pharm Sci 25:81–89CrossRefGoogle Scholar
  25. Ruozi B, Tosi G, Leo E (2007) Application of atomic force microscopy to characterize liposomes as drug and gene carriers. Talanta 73:12–22CrossRefGoogle Scholar
  26. Sharma A, Sharma US (1997) Liposomes in drug delivery: progress and limitations. Int J Pharm 154:123–140CrossRefGoogle Scholar
  27. Shibata-Sekia T, Masai J, Tagawa T (1996) In-situ atomic force microscopy study of lipid vesicles adsorbed on a substrate. Thin Solid Films 273:297–303CrossRefGoogle Scholar
  28. Smith HJ, Smith JR, Multi-drug liposomes to treat tumors, Patent Application Publication, Pub. No.: US 2012/0231066 A1, United StatesGoogle Scholar
  29. Wang ES, Straus DJ (2003) Intensive chemotherapy with cyclophosphamide, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC) for human immunodeficiency virus-associated Burkitt lymphoma. Cancer 98:1196–1205CrossRefGoogle Scholar
  30. Yamanaka R, Shinbo Y, Sano M (2007) Salvage therapy and late neurotoxicity in patients with recurrent primary CNS lymphoma treated with a modified ProMACE-MOPP hybrid regimen. Leuk Lymphoma 48:1119–1126CrossRefGoogle Scholar
  31. Zhong Q, Inniss D, Kjoller K, Elings VB (1993) Fractured polymer/silica fiber surface studied by tapping mode atomic force microscopy. Surf Sci Lett 290:688–692Google Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2016

Authors and Affiliations

  1. 1.Department of Materials Chemistry and Chemical Technology, Institute of ChemistryUniversity of SilesiaKatowicePoland

Personalised recommendations