Insights into the multi-equilibrium, superstructure system based on β-cyclodextrin and a highly water soluble guest.

Elgte Elmin B De Paula, Frederico B De Sousa, Júlio César C Da Silva, Flaviana R Fernandes, Maria Norma Melo, Frédéric Frézard, Richard M Grazul, Rubén D Sinisterra, Flávia C Machado

Núcleo de Espectroscopia e Estrutura Molecular, Departamento de Química, Universidade Federal de Juiz de Fora, Campus Universitário s/n, Martelos, Juiz de Fora, MG, 36036-900, Brazil.

International journal of pharmaceutics 2012 Dec 15

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Pentamidine isethionate (PNT) is an antiprotozoal active in many cases of leishmaniasis, despite the present limitations including high toxicity and parenteral administration. In the present work, a PNT encapsulation strategy into β-cyclodextrin cavity at 1:1 and 2:1 (βCD:PNT) molar ratios was used in order to improve the drug's physical and chemical properties. Combining thermodynamic and structural approaches such as isothermal titration calorimetry (ITC), electrospray ionization mass spectrometry (ESI-MS) and nuclear magnetic resonance ((1)H NMR, and ROESY) the inclusion process and the thermodynamics parameters were identified. ITC and ESI-MS experimental data suggest the simultaneous formation of different supramolecular complexes in solution. Moreover, NMR data are in accordance with these results, suggesting a deep inclusion of PNT into the βCD cavity, through correlations observed in 2D ROESY contour maps. The systems were also characterized by FTIR, TG/DTA and SEM. These techniques indicate the formation of inclusion complex in the solid state. In vivo PNT activity was evaluated orally in mice. The inclusion complex showed a significant reduction of parasite load compared to free PNT. Copyright © 2012 Elsevier B.V. All rights reserved.

Citation

Elgte Elmin B De Paula, Frederico B De Sousa, Júlio César C Da Silva, Flaviana R Fernandes, Maria Norma Melo, Frédéric Frézard, Richard M Grazul, Rubén D Sinisterra, Flávia C Machado. Insights into the multi-equilibrium, superstructure system based on β-cyclodextrin and a highly water soluble guest. International journal of pharmaceutics. 2012 Dec 15;439(1-2):207-15