title: Insights into the multi-equilibrium, superstructure system based on β-cyclodextrin and a highly water soluble guest.
abstract: 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.
authors.affiliation: 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.
authors.forename: Elgte Elmin B
authors.initials: EE
authors.lastname: De Paula
authors.forename: Frederico B
authors.initials: FB
authors.lastname: De Sousa
authors.forename: Júlio César C
authors.initials: JC
authors.lastname: Da Silva
authors.forename: Flaviana R
authors.initials: FR
authors.lastname: Fernandes
authors.forename: Maria Norma
authors.initials: MN
authors.lastname: Melo
authors.forename: Frédéric
authors.initials: F
authors.lastname: Frézard
authors.forename: Richard M
authors.initials: RM
authors.lastname: Grazul
authors.forename: Rubén D
authors.initials: RD
authors.lastname: Sinisterra
authors.forename: Flávia C
authors.initials: FC
authors.lastname: Machado
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000737:chemistry*; D005260:Female; D018314:Leishmania infantum; D007898:Leishmaniasis, Visceral / Q000188:drug therapy / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D059208:Parasite Load; D010419:Pentamidine / Q000008:administration & dosage / Q000737:chemistry*; D012995:Solubility; D014867:Water / Q000737:chemistry; D047392:beta-Cyclodextrins / Q000008:administration & dosage / Q000737:chemistry*
chemical_list: D000981:Antiprotozoal Agents; D047392:beta-Cyclodextrins; D014867:Water; D010419:Pentamidine; C031215:betadex