Drug–matrix interactions in nanostructured materials containing fluoxetine using sol-gel titanium oxide as a matrix


Titanium oxide matrix was prepared by sol-gel adding fluoxetine [Prozac (C17H18NF3O)] during the reaction of gelation. This nanostructured material was studied by Fourier transform infrared (FTIR) spectroscopy, N2 adsorption, and x-ray diffraction to detect the interaction between the drug and the matrix. The complex nature of FTIR signals for the matrix and the drug did not allow observation of the interactions; however, using the density functional theory formalism, two stable complexes are suggested to be formed on the drug–matrix system. Both complexes are formed through H bond interactions involving the amine group in fluoxetine and the hydroxylated sites in titanium xerogel. They were found to be energetically stable and independent of the titanium model core cluster used in the calculations.

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  1. 1.

    P. Kinam: Nanotechnology: What it can do for drug delivery. J. Control. Release 3, 1201 (2007).

    Google Scholar 

  2. 2.

    M. Vallet-Regi, A. Ramila del Real, and R.P. Perez-Pariente: Nanostructure of bioactive sol-gel glasses and organic-inorganic hybrids. J. Chem. Mater. 13, 308 (2005).

    Article  Google Scholar 

  3. 3.

    A. Vinu, P. Dhanshri Sawant, K. Ariga, K.Z. Hossain, S.B. Halligudi, M. Hartmann, and M. Nomura: Direct synthesis of well-ordered and unusually reactive FeSBA-15 mesoporous molecular sieves. Chem. Mater. 17, 4577 (2005).

    Article  Google Scholar 

  4. 4.

    T. López, E. Ortiz-Islas, J. Manjarrez, F. Reynoso, R. Sepulveda, A.R.D. González: Structural, optical and vibrational properties of sol–gel titania valproic acid reservoirs. Opt. Mater. 29, 70 (2006).

    Article  Google Scholar 

  5. 5.

    P. Horcajada, A. Ramila, G. Ferey, and M. Vallet-Regi: Tissue regeneration: A new property of mesoporous materials. Solid State Sci. 8, 1243 (2005).

    Article  Google Scholar 

  6. 6.

    M.V. Cabañas, J. Peña, J. Román, and M. Vallet-Regí: Tailoring vancomycin release from ß-TCP/agarose scaffolds. Eur. J. Pharm. Sci. 37, 3 (2009).

    Article  Google Scholar 

  7. 7.

    S. Benitas: Methods and Industrial Applications (Marcel Dekker Inc, New York, 1996), pp. 45–80.

    Google Scholar 

  8. 8.

    V.B. Patravale, A.A. Date, and R.M. Kulkarni: Nanosuspensions a promising drug delivery strategy. J. Pharm. Pharmacol. 56, 827 (2004).

    CAS  Article  Google Scholar 

  9. 9.

    M. González: Obtención y estudio de las propiedades química-físicas de materiales nanoestructurados que contienen diferentes fármacos de interés. Ph.D.Thesis, University of Havana, 2009.

    Google Scholar 

  10. 10.

    E.P. Barret, L.G. Joyner, and P.P. Halenda: The determination of pore volume and area distributions in porous substances. J. Am. Chem. Soc. 73, 373 (1951).

    Article  Google Scholar 

  11. 11.

    Gaussian 03. (2004) Revision D.01, M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman, J.A. Montgomery Jr., T. Vreven, K.N. Kudin, J.C. Burant, J.M. Millam, S.S. Iyengar, J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G.A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J.E. Knox, H.P. Hratchian, J.B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R.E. Stratmann, O. Yazyev, A.J. Austin, R. Cammi, C. Pomelli, J.W. Ochterski, P.Y. Ayala, K. Morokuma, G.A. Voth, P. Salvador, J.J. Dannenberg, V.G. Zakrzewski, S. Dapprich, A.D. Daniels, M.C. Strain, O. Farkas, D.K. Malick, A.D. Rabuck, K. Raghavachari, J.B. Foresman, J.V. Ortiz, Q. Cui, A.G. Baboul, S. Clifford, J. Cioslowski, B.B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R.L. Martin, D.J. Fox, T. Keith, M.A. Al-Laham, C.Y. Peng, A. Nanayakkara, M. Challacombe, P.M. W. Gill, B. Johnson, W. Chen, M.W. Wong, C. Gonzalez, and J.A. Pople, Gaussian, Inc., Wallingford CT.

  12. 12.

    A. D. Becke. Density functional thermochemistry. III. The role of exact exchange. J. Chem. Phys. 98, 5648 (1993).

    CAS  Article  Google Scholar 

  13. 13.

    T.H. Dunning Jr. and P.J. Hay: Modern Theoretical Chemistry, edited by H. F. Schaefer III (Plenum, New York. 1976), pp. 341–450.

  14. 14.

    (a) K. Fukui: Role of frontier orbitals in chemical reactions. Science. 218, 747 (1982). (b) R.G. Parr and W. Yang: Density functional approach to the frontier-electron theory of chemical reactivity. J. Am. Chem. Soc. 106, 4049 (1984).

    CAS  Article  Google Scholar 

  15. 15.

    B. Delley: An all-electron numerical method for solving the local density functional for polyatomic molecules. J. Chem. Phys. 92, 508 (1990).

    CAS  Article  Google Scholar 

  16. 16.

    B. Delley: From molecules to solids with the DMol3 approach. J. Chem. Phys. 113, 7756 (2000).

    CAS  Article  Google Scholar 

  17. 17.

    W. Yang and W.J. Mortier: The use of global and local molecular parameters for the analysis of the gas-phase basicity of amines. J. Am. Chem. Soc. 108, 5708 (1986).

    CAS  Article  Google Scholar 

  18. 18.

    F.L. Hirshfeld: Bonded-atom fragments for describing molecular charge densities. Theor. Chim. Acta. 44, 129 (1977).

    CAS  Article  Google Scholar 

  19. 19.

    M. Gonzalez and J. Rieumont. Obtaining by sol-gel of nanostructured materials loaded with fluoxetine kinetic considerations. LabCiencia con noticias técnicas del laboratorio 1, 3–6 (2011).

    Google Scholar 

  20. 20.

    T. Bezrodna and G. Puchkovska: IR-analysis of H-bonded H2O on the pure TiO2 surface. J. Mol. Struct. J. Mol. Struct. 70, 175 (2004).

    Article  Google Scholar 

  21. 21.

    M. Tchoul, S.P. Fillery, H. Koerner, L.F. Drummy, F.T. Oyerokun, P.A. Mirau, M.F. Durstock, and R.A. Vaia: Assemblies of titanium dioxide-polystyrene hybrid nanoparticles for dielectric applications. Chem. Mater. 22, 1749 (2010).

    CAS  Article  Google Scholar 

  22. 22.

    E. Poulios, E. Micropoulou, R. Panou, and E. Kostopoulou: Kinetic study of the photocatalytic recovery of Pt from aqueous solution by TiO2, in a closed-loop reactor. Appl. Catal. B. 4, 1345 (2003).

    Google Scholar 

  23. 23.

    B. Balasubramanian, K.L. Kraemer, N.A. Reding, R. Skomski, S. Ducharme, and D.J. Sellmyer: Synthesis of monodisperse TiO2 paraffin core-shell nanoparticles for improved dielectric properties. ACS Nano 4(4), 1893 (2010).

    CAS  Article  Google Scholar 

  24. 24.

    V. Gomes, M.B. Fernanda, and S. Gomes: Principias metodos de caracterizacao de porosidade de resinas a base de divinilbenzeno. Quim. Nova 24(6), 808 (2001).

    Google Scholar 

  25. 25.

    S. Brunnauer, P. Emmet, and E. Teller: Adsorption of gases in multimolecular layers. J. Am. Chem. Soc. 60, 309 (1938).

    Article  Google Scholar 

  26. 26.

    Y. Okuno: Theoretical investigation of the mechanism of the Baeyer-Villiger reaction in nonpolar solvents. Chemistry 3, 212 (1997).

    CAS  Article  Google Scholar 

  27. 27.

    S. Watson, J. Beydoun, and R. Amal: Preparation of nanosized crystalline TiO2 particles at low temperature for photocatalysis. J. Nanopart. Res. 6, 193 (2004).

    CAS  Article  Google Scholar 

  28. 28.

    J. Dzubiella and J-P. Hansen: Electric-field-controlled water and ion permeation of a hydrophobic nanopore. J. Phys. Chem. B 122, 4702 (2005).

    Google Scholar 

  29. 29.

    C. Aguado, B. Pérez, M. Ugarte, and L.R. Desviat: Analysis of the effect of tetrahydrobiopterin on PAH gene expression in hepatoma cells. FEBS Lett. 7, 1697 (2006).

    Article  Google Scholar 

  30. 30.

    A. Galano: Influence of silicon defects on the adsorption of thiophene-like compounds on polycyclic aromatic hydrocarbons: A theoretical study using thiophene + coronene as the simplest mode. J. Phys. Chem. A 111, 4726 (2007).

    CAS  Article  Google Scholar 

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The author thanks the Red of Macrouniversidad, Autonomous Metropolitan University (UAM), National Institute of Neurology and Neurosurgery (INNN), México and Foncicyt project No. 96095 for financial support and also to M.S. D. Aguilar for the technical support.

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Correspondence to Mayra González.

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González, M., Rieumont, J., Figueras, F. et al. Drug–matrix interactions in nanostructured materials containing fluoxetine using sol-gel titanium oxide as a matrix. Journal of Materials Research 26, 2871–2876 (2011). https://doi.org/10.1557/jmr.2011.266

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  • Structural
  • Sol-gel
  • Nanostructure