Obtenção de parâmetros físico-químicos de hidroxiquinonas e sua formulação em quitosana

Abstract

Quinones are widespread in nature and play important biochemical and physiological roles. The transposition over plasmatic membranes is a requisite for one molecule to reach plasmatic concentrations capable to reproduce their biological effect. Physico-chemical parameters have an important impact on pharmacokinetic and metabolic fate of the biologically active compounds in the body, and so, a good understanding of these properties, coupled with their measurement and prediction are crucial for the understanding of a biological mechanism of action. One of main physico-chemical properties of micromolecules able to modify the pharmacotherapeutic profile is the ionization coefficient, expressed by pKa, which indicates the relative contribution degree of neutral and ionized species from ionizable groups. Several quinones can be degradated, when exposed to environmental factors like light and heat. The incorporation onto some matrices can contribute to their stabilization. Chitosan is one of possible choices. In the present work, the pKa of four differently substituted 2-hydroxynaphtoquinones were measured, in a mixed ethanolic/aqueous buffer, using hybrid pH/UV titration and voltametric titration. The adsorption, on chitosan, of 3 naphtoquinones sodium salts and their quantification using spectrophotometric techniques were also performed. Chemical modified electrodes were employed in this work in the attempt to verify a possible change in the lapachol electrochemical behavior in order to facilitate its quantification. Isolapachol (pKa<6) showed to be more acid than lapachol (pKa>6) and the inactive methylamino derivatives, with 2 pKas, one related to the enol and the other to the ammonium salt are zwitterionic in the physiological pH, fact that can preclude its entrance in the cell, causing its biological inactivity. Those parameters are important for the understanding of the mechanism of biological action. In the study with the salts of quinones, the calibration plots were obtained with R values above 0.999 for each salt. With chitosan, it was verified that the sodium salts of lapachol and isolapachol suffer adsorption on chitosan, through the visible UV-vis absorbance decrease. For the lapachol salt, the absorbance was reduced in about 60% (Absinitial = 1.825 e Absfinal = 0.732). After 2.5 hours of agitation, concentration changes from 2 x 10-4 mol L-1 to 7.5 x 10-5 mol L-1. 30 mg of chitosan adsorbed 0.330 mg of lapachol salt. For isolapachol, a lower adsorption was observed (~10 %, Absinitial = 2.057 e Absfinal = 1.862), with a salt final concentration of 1.8 x 10-4 mol L-1 (0,475 mg). Differently from these two quinones, the salt of di-hydrolapachol was not adsorbed on chitosan. Its electronic spectrum did not change after contact with the biopolymer. Structural factors and the acidity differences, indicated by pKa, account for these variations in terms of adsorption on chitosan. Using modified electrodes with glassy-carbon surface-immobilized metallic complexes, any significant modification on the electrochemical behavior of lapachol was observed.