Inclusion Complex between Usnic of Acid and b-cyclodextrin: Characterization and Antimicrobial Activity
Lira, M.C.B1,2; Cortes, M.E.3 Teixeira, K.I.R. 3; Rubén D. Sinisterra4; Santos-Magalhães, N.S1,2,5
1Laboratório de Imunopatologia Keizo-Asami (LIKA); 2Programa de Pós-Graduação em Ciências Farmacêuticas; 3Faculdade de Odontologia,UFMG; 4Dep. Química, UFMG; 5Dep. Bioquímica, UFPE
The aim of this study was to develop, characterize and evaluate the antimicrobial activity of usnic acid (UA) and 2-hydroxypropyl-b-cyclodextrin (HPb-CD) inclusion complexes. UA:HPb-CD complexes were prepared using different techniques as physical mixture, co-precipitation and freeze-drying. The UA:HPb-CD was characterized using standard thermal analysis (DSC and TG), X-ray diffractometry, and Infrared, H1 and 2D-ROESY NMR spectroscopy. The stoichiometry of the complexes was investigated through the phase solubility method. A dissolution test of free UA and UA:HPb-CD was performed at pH 7.4. The antimicrobial activity of UA:HPb-CD was evaluated on Streptococcus mutas (ATCC 25175), Enterococcus faecalis (ATCC 14 508) and Actibobacillus actinomycetecomitans (Y4-FDC) from UFRJ- Brazil, using disc-diffusion method. UA:HPb-CD inclusion complex was tested in comparison with free UA (75 mg/ml). The freeze-dried UA:HPb-CD product presented NMR and IR spectral modifications in comparison with UA or HPb-CD spectra. A highest degree of amorphization observed in X-ray and the disappearance of UA fusion peak in DSC spectra confirm the formation of UA:HPb-CD inclusion complex. The phase solubility diagram showed an AL curve with an apparent formation constant of 1.14 x 103 M-1, calculated by assuming a 1:1 stoichiometry ratio. This suggested that van der Walls and hydrogen bond interactions probably occurred. The UA amount dissolved from inclusion complex system was about 50% higher than free UA. The UA:HPb-CD inhibitory zone diameter was: S. mutans 9.3 ± 1.1 and 9.6 ± 0.5; E. faecalis 15.0 ± 0.5 and 13.6 ± 0.5; A. actinomycetecomitans 15.6 ± 1.1 and 13.6 ± 2.5 for the binary complex and free UA, respectively. In conclusion, UA:HPb-CD inclusion complexes were obtained and no significant differences on the antimicrobial activity were observed between the free UA and UA:HPb-CD, supporting that the drug shown an antimicrobial activity and the inclusion process has no interference on its immediate activity.
Supported by: CNPq/MCT.
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