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.
Similar content being viewed by others
References
Loftsson, T., Brewester, M.: Pharmaceutical applications of cyclodextrins. 1. Drug solubilization and stabilization. J. Pharm. Sci. 85, 1017–1025 (1996)
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)
Martin Del Valle, E.M.: Cyclodextrins and their uses: a review. Process Biochem. 39, 1033–1046 (2004)
McCormack, B., Gregoriadis, G.: Drugs in cyclodextrins in liposomes: a novel concept in drug delivery. Int. J. Pharm. 112, 249–258 (1994)
McCormack, B., Gregoriadis, G.: Entrapment of cyclodextrin drug complexes into liposomes: potential advantages in drug delivery. J. Drug Target. 2, 449–454 (1994)
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)
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)
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)
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)
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)
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)
Job, P.: Formation and stability of inorganic complexes in solution. Anal. Chim. 9, 113–203 (1928)
Johnson, C.S.: Diffusion ordered nuclear magnetic resonance spectroscopy: principles and applications. Prog. Nucl. Reson. Spectrosc. 34, 203–256 (1999)
Cameron, K.S., Fielding, L.: NMR diffusion coefficient study of steroid–cyclodextrin inclusion complexes. Magn. Reson. Chem. 40, S106–S109 (2002)
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)
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)
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)
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)
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)
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)
Soubias, O., Gawrisch, K.: Probing specific lipid–protein interaction by saturation transfer difference NMR spectroscopy. J. Am. Chem. Soc. 127, 13110–13111 (2005)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10847-015-0483-1