Skip to main content
Log in

Preparation and characterization of a ternary inclusion complex comprising the norfloxacin/β-cyclodextrin complex incorporated in a liposome

  • Original Article
  • Published:
Journal of Inclusion Phenomena and Macrocyclic Chemistry Aims and scope Submit manuscript

Abstract

A liposome containing the β-cyclodextrin (β-CD) complex of norfloxacin (NFLX) was prepared and its ternary structure characterized. Structural information about the NFLX/β-CD complex was obtained by infrared spectroscopy and powder X-ray diffraction. Nuclear magnetic resonance (NMR) ROESY experimental results confirmed the inclusion structure, with the results well matching those of molecular docking studies. The stoichiometry and the association constant of the complex were also determined. Free multilamellar vesicles composed of soybean phospholipids and cholesterol as membrane materials were prepared and loaded with NFLX, β-CD, and the NFLX/β-CD complex. Diffusion coefficients measured by 19F NMR spectroscopy were compared. In addition, saturation transfer difference NMR experiments were performed to elucidate the structural differences of these liposomes. The results confirmed the formation of the ternary inclusion system comprising the liposome and the NFLX/β-CD complex. Transmission electron micrographs showed the morphological features and particle size differences of these liposomes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

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

Similar content being viewed by others

References

  1. Loftsson, T., Brewester, M.: Pharmaceutical applications of cyclodextrins. 1. Drug solubilization and stabilization. J. Pharm. Sci. 85, 1017–1025 (1996)

    Article  CAS  Google Scholar 

  2. Song, L.X., Bai, L., Xu, X.M., He, J., Pan, S.Z.: Inclusion complexation, encapsulation interaction and inclusion number in cyclodextrin chemistry. Coord. Chem. Rev. 253, 1276–1284 (2009)

    Article  CAS  Google Scholar 

  3. Martin Del Valle, E.M.: Cyclodextrins and their uses: a review. Process Biochem. 39, 1033–1046 (2004)

    Article  Google Scholar 

  4. McCormack, B., Gregoriadis, G.: Drugs in cyclodextrins in liposomes: a novel concept in drug delivery. Int. J. Pharm. 112, 249–258 (1994)

    Article  CAS  Google Scholar 

  5. McCormack, B., Gregoriadis, G.: Entrapment of cyclodextrin drug complexes into liposomes: potential advantages in drug delivery. J. Drug Target. 2, 449–454 (1994)

    Article  CAS  Google Scholar 

  6. Loukas, Y.L., Vraka, V., Gregoriadis, G.: Drugs in cyclodextrins in liposomes: a novel approach to the chemical stability of drugs sensitive to hydrolysis. Int. J. Pharm. 162, 137–142 (1998)

    Article  CAS  Google Scholar 

  7. Cabec, L.F., Figueiredo, I.M., Paula, E., Marsaioli, A.J.: Prilocaine–cyclodextrin–liposome: effect of pH variations on the encapsulation and topology of a ternary complex using 1HNMR. Magn. Reson. Chem. 49, 295–300 (2011)

    Article  Google Scholar 

  8. Loukas, Y.L., Jayasekera, P., Gregoriadis, G.: Novel liposome-based multicomponent systems for the protection of photolabile agents. Int. J. Pharm. 117, 85–94 (1995)

    Article  CAS  Google Scholar 

  9. Schmidt, A.K., Cottaz, S., Driguez, H., Schulz, G.E.: Structure of cyclodextrin glycosyltransferase complexed with a derivative of its main product β-cyclodextrin. Biochemistry 37, 5909–5915 (1998)

    Article  CAS  Google Scholar 

  10. Frisch, M.J., Trucks, G.W., Schlegel, H.B., Scuseria, G.E., Robb, M.A., Cheeseman, J.R., et al.: Gaussian 03, Revision-B.03. Gaussian, Inc., Pittsburgh (2003)

    Google Scholar 

  11. Morris, G.M., Goodsell, D.S., Halliday, R.S., Huey, R., Hart, W.E., Belew, R.K., Olson, A.J.: Automated docking using a Lamarckian genetic algorithm and empirical binding free energy function. J. Comput. Chem. 19, 1639–1662 (1998)

    Article  CAS  Google Scholar 

  12. Job, P.: Formation and stability of inorganic complexes in solution. Anal. Chim. 9, 113–203 (1928)

    CAS  Google Scholar 

  13. Johnson, C.S.: Diffusion ordered nuclear magnetic resonance spectroscopy: principles and applications. Prog. Nucl. Reson. Spectrosc. 34, 203–256 (1999)

    Article  CAS  Google Scholar 

  14. Cameron, K.S., Fielding, L.: NMR diffusion coefficient study of steroid–cyclodextrin inclusion complexes. Magn. Reson. Chem. 40, S106–S109 (2002)

    Article  CAS  Google Scholar 

  15. Jullian, C., Miranda, S., Zapata-Torres, G., Mendizabal, F., Olea-Azar, C.: Studies of inclusion complexes of natural and modified cyclodextrin with (+) catechin by NMR and molecular modeling. Bioorg. Med. Chem. 15, 3217–3224 (2007)

    Article  CAS  Google Scholar 

  16. Meinecke, B., Meyer, B.: Determination of the binding specificity of an integral membrane protein by saturation transfer difference NMR: RGD peptide ligands binding to integrin αIIbβ3. J. Med. Chem. 44, 3059–3065 (2001)

    Article  CAS  Google Scholar 

  17. Mayer, M., Meyer, B.: Group epitope mapping by saturation transfer difference NMR to identify segments of a ligand in direct contact with a protein receptor. J. Am. Chem. Soc. 123, 6108–6117 (2001)

    Article  CAS  Google Scholar 

  18. Mayer, M., James, T.L.: Detecting ligand binding to a small RNA target via saturation transfer difference NMR experiments in D2O and H2O. J. Am. Chem. Soc. 124, 13376–13377 (2002)

    Article  CAS  Google Scholar 

  19. Sandstro, C., Berteau, O., Gemma, E., Oscarson, S., Kenne, L., Gronenborn, A.M.: Atomic mapping of the interactions between the antiviral agent cyanovirin-N and oligomannosides by saturation-transfer difference NMR. Biochemistry 43, 13926–13931 (2004)

    Article  Google Scholar 

  20. Chatterjee, C., Majumder, B., Mukhopadhyay, C.: Pulsed-field gradient and saturation transfer difference NMR study of enkephalins in the ganglioside GM1 micelle. J. Phys. Chem. B 108, 7430–7436 (2004)

    Article  CAS  Google Scholar 

  21. Soubias, O., Gawrisch, K.: Probing specific lipid–protein interaction by saturation transfer difference NMR spectroscopy. J. Am. Chem. Soc. 127, 13110–13111 (2005)

    Article  CAS  Google Scholar 

  22. Herfurth, L., Ernst, B., Wagner, B., Ricklin, D., Strasser, D.S., Magnani, J.L., et al.: Comparative epitope mapping with saturation transfer difference NMR of sialyl Lewis a compounds and derivatives bound to a monoclonal antibody. J. Med. Chem. 48, 6879–6886 (2005)

    Article  CAS  Google Scholar 

  23. Schauff, S., Friebolin, V., Grynbaum, M.D., Meyer, C., Albert, K.: Monitoring the interactions of tocopherol homologues with reversed-phase stationary HPLC phases by 1H suspended-state saturation transfer difference high-resolution magic angle spinning NMR spectroscopy. Anal. Chem. 79, 8323–8326 (2007)

    Article  CAS  Google Scholar 

  24. Milojevic, J., Esposito, V., Das, R., Melacini, G.: Understanding the molecular basis for the inhibition of the Alzheimer’s Aβ-peptide oligomerization by human serum albumin using saturation transfer difference and off-resonance relaxation NMR spectroscopy. J. Chem. Soc. 129, 4282–4290 (2007)

    Article  CAS  Google Scholar 

  25. Shirzadi, A., Simpson, M.J., Xu, Y., Simpson, A.J.: Application of saturation transfer double difference NMR to elucidate the mechanistic interactions of pesticides with humic acid. Environ. Sci. Technol. 42, 1084–1090 (2008)

    Article  CAS  Google Scholar 

  26. Feher, K., Groves, P., Batta, G., Jimenez-Barbero, J., Golland, C.M., Kover, K.E.: Competition saturation transfer difference experiments improved with isotope editing and filtering schemes in NMR-based screening. J. Am. Chem. Soc. 130, 17148–17153 (2008)

    Article  CAS  Google Scholar 

  27. Huang, H., Milojevic, J., Melacini, G.: Analysis and optimization of saturation transfer difference NMR experiments designed to map early self-association events in amyloidogenic peptides. J. Phys. Chem. B 112, 5795–5802 (2008)

    Article  CAS  Google Scholar 

  28. Pereira, A., Pfeifer, T.A., Grigliatti, T.A., Andersen, R.J.: Functional cell-based screening and saturation transfer double-difference NMR have identified haplosamate A as a cannabinoid receptor agonist. ACS Chem. Biol. 4, 139–144 (2009)

    Article  CAS  Google Scholar 

  29. Szczygiel, A., Timmermans, L., Fritzinger, B., Martins, J.C.: Widening the view on dispersant–pigment interactions in colloidal dispersions with saturation transfer difference NMR spectroscopy. J. Am. Chem. Soc. 131, 17756–17758 (2009)

    Article  CAS  Google Scholar 

  30. Longstaffe, J., Simpson, M., Maas, W., Simpson, A.: Identifying components in dissolved humic acid that bind organofluorine contaminants using 1H{19F} reverse heteronuclear saturation transfer difference NMR spectroscopy. Environ. Sci. Technol. 44, 5476–5482 (2010)

    Article  CAS  Google Scholar 

  31. Viegas, A., Manso, J.O., Corvo, M.C., Manuel, M., Marques, B., Cabrita, E.J.: Binding of ibuprofen, ketorolac, and diclofenac to COX-1 and COX-2 studied by saturation transfer difference NMR. J. Med. Chem. 54, 8555–8562 (2011)

    Article  CAS  Google Scholar 

  32. Cabec, L.F., Fernandes, S.A., Paula, E., Marsaioli, A.J.: Topology of a ternary complex (proparacaine–β-cyclodextrin–liposome) by STD NMR. Magn. Reson. Chem. 46, 832–837 (2008)

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Yinghua Liu or Xianrui Yuan.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, Y., Yuan, X. Preparation and characterization of a ternary inclusion complex comprising the norfloxacin/β-cyclodextrin complex incorporated in a liposome. J Incl Phenom Macrocycl Chem 82, 311–321 (2015). https://doi.org/10.1007/s10847-015-0483-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10847-015-0483-1

Keywords

Navigation