Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 439, Issue 1-2, Pages 207-215Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2012.09.039
Keywords
Supramolecular complex; beta-cyclodextrin; Pentamidine; Multi-equilibrium; Leishmaniasis; In vivo experiments
Categories
Funding
- CNPq
- CAPES
- FAPEMIG [PRONEX 526/07]
- Rede Mineira de Quimica (RQ-MG)
- LNLS - Brazilian Synchrotron Light Laboratory/MCT
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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 beta-cyclodextrin cavity at 1: 1 and 2: 1 (beta CD: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 (H-1 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 beta CD 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. (C) 2012 Elsevier B. V. All rights reserved.
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