DESENVOLVIMENTO E AVALIAÇÃO DE UM SISTEMA NANOESTRUTURADO CONTENDO DISSELENETO DE DIFENILA

Abstract

The diphenyl diselenide, (PhSe)2, is a simple selenium organocompound known for its pharmacological and toxicological effects, however, its clinical application is limited by its low aqueous solubility, which results in low bioavailability, restricting its efficacy. To overcome these limitations, this study developed polymeric nanoparticles (Nps) containing (PhSe)2 by the method of emulsification-solvent evaporation.The high-performance liquid chromatography (HPLC) coupled to a photodiode detector (PDA) was analytical method used for quantification of (PhSe)2 present in the nanoparticles. The method was validated according to current norms, mobile phase consisted of methanol and acidified water (90:10, v/v), flow 1 mL/min with detection at 240 nm. Nanoparticles of poly (lactic acid) (PLA) containing (PhSe)2 were successfully obtained, showed spherical shape and an encapsulation efficiency and mean size close to 90%, and 220 nm, respectively. The zeta potential of the formulation was -23 mV, a value that theoretically ensures physicochemical stability of the particles. The infrared analysis, X-ray diffraction, differential scanning calorimetry and thermogravimetric showed that the nanoencapsulation process promoted drug amorphation and interaction of (PhSe)2 with the polymeric matrix. The stability study shows that Nps in suspension did not show stability in the 7 days test, whereas the lyophilized Nps were stable over the 3month study both at room temperature, the chilled and frozen. The in vitro release study showed that the end of the 192 h about 61% of (PhSe)2encapsulated was released and that this release occurred by two constants, a fast and other slowly, suggesting a second order kinetics. Through the antioxidant assay was possible to observe that the process of nanoencapsulation did not alter the antioxidant potential of (PhSe)2, since after 48 hours the nanoparticles showed inhibitory capacity similar to (PhSe)2 free.In the erythrocyte cytotoxicity assay, Nps-(PhSe)2 showed lower toxicity on erythrocyte than free (PhSe)2. Finally the NPs were tested against the tumor lines (B16-F10 and HEp-2), and the results obtained were promising, since the nanoparticles of (PhSe)2 maintained the antitumor property of the compound. Thus, the PLA nanoparticles demonstrated to be potential carriers for (PhSe)2, with adequate physicochemical characteristics, lower cytotoxicity on normal cells and maintenance of antioxidant and antitumor activity.