Hydroxymethylnitrofurazone:Dimethyl-beta-cyclodextrin Inclusion Complex: A Physical-Chemistry Characterization

Author(s)

Grillo, Renato ^[1] ; Silva Melo, Nathalie Ferreira ^[1] ; Moraes, Carolina Morales ^[2] ; Rosa, Andre Henrique ^[1] ; Frutuoso Roveda, Jose Arnaldo ^[1] ; Menezes, Carla M. S. ^[3] ; Ferreira, Elizabeth Igne ^[3] ; Fraceto, Leonardo Fernandes ^{[2, 1]}

Affiliation

^[1] State Univ Sao Paulo, Dept Environm Engn, BR-18087180 Sorocaba, SP - Brazil

^[2] Univ Estadual Campinas, Inst Biol, Dept Biochem, Campinas, SP - Brazil

^[3] Univ Sao Paulo, Fac Pharmaceut Sci, LAPEN, Sao Paulo - Brazil

• Document type: Journal article
• Source: Journal of Biological Physics; v. 33, n. 5-6, p. 445-453, DEC 2007.
• Web of Science Citations: 12

Abstract

Hydroxymethylnitrofurazone (NFOH) is active against Trypanosoma cruzi; however, its low solubility and high toxicity precludes its current use in treatment of parasitosis. Cyclodextrin can be used as a drug carrier system, as it is able to form inclusion (host-guest) complexes with a wide variety of organic (guest) molecules. Several reports have shown the interesting use of modified beta-cyclodextrins in pharmaceutical formulation, to improve the bioavailability of drugs and to decrease their toxicity. The aim of this work was to characterize inclusion complexes formed between NFOH and dimethyl-beta-cyclodextrin (DM-beta-CD) by complexation/release kinetics and solubility isotherm experiments using ultraviolet (UV)-visible spectrophotometry and by the measurement of the dynamics information obtained from T (1) relaxation times and diffusion (DOSY) experiments using nuclear magnetic resonance (NMR) spectroscopy. The complex was prepared at different NFOH and DM-beta-CD molar ratios. The UV-visible measurements were recorded in a spectrophotometer, and NMR experiments were recorded at 20 degrees C on a NMR spectrometer (Varian Inova) operating at 500 MHz. Longitudinal relaxation times were obtained by the conventional inversion-recovery method and the DOSY experiments were carried out using the BPPSTE sequence. The kinetics of complexation revealed that 30 h is enough for stabilization of the NFOH absorbance in presence of cyclodextrin. Solubility isotherm studies show a favorable complexation and increase in solubility when NFOH interacts with cyclodextrin. The analysis of the NMR-derived diffusion coefficients and T (1) relaxation times shows that in the presence of DM-beta-CD, NFOH decreases its mobility in solution, indicating that this antichagasic compound interacts with the cyclodextrin cavity. The release kinetics assays showed that NFOH changes its release profile when in the presence of cyclodextrin due to complexation. This study was focused on the physicochemical characterization of drug-delivery formulations that may serve as potentially new therapeutic options for the treatment of Chagas' disease. (AU)

• FAPESP's process: 05/03045-9 - Development of inclusion complexes between antichagasic compounds and cyclodextrins
• Grantee: Leonardo Fernandes Fraceto
• Support Opportunities: Regular Research Grants