Antitumor action of diphenyl diselenide nanocapsules: In vitro assessments and preclinical evidence in an animal model of glioblastoma multiforme

Background: Gliomas are the most aggressive malignant tumors of the central nervous system. The diphenyl diselenide [(PhSe)(2)] is an organoselenium compound that has multiple pharmacological properties. Previous reports showed that (PhSe)(2) nanoencapsulation potentiates its in vitro antitumoral action and reduces its toxicity. Objective: In this sense, the current study was designed to further evaluate the (PhSe)(2) antitumoral effect by a set of in vitro techniques using a glioma cell line as well as by an animal model of gliobastoma. Methods: For the in vitro tests, the cell viability, propidium iodide uptake and nitrite levels of rat glioma C6 cells were determined after incubation with free (PhSe)(2) or (PhSe)(2)-loaded nanocapsules (NC). The glioblastoma model was induced by implantation of C6 glioma cells in the right striatum of rats. Following, animals were submitted to a repeated intragastric administration treatment with (PhSe)(2) or NC (PhSe)(2) (1 mg/kg/day for 15 days) to assess the possible antitumor effect. Main findings: Both compound forms decreased the C6 glioma cells viability without causing any effect in astrocytes cells (healthy control). Importantly, the NC (PhSe)(2) had superior cytotoxic effect than its free form and increased the nitrite content. Independent of the (PhSe)(2) forms, the intragastric treatment reduced brain tumor size and caused neither alteration in the plasma renal and hepatic markers of function nor in the parameters of oxidative balance in brain, liver and kidneys. Principal conclusions: The (PhSe)(2) nanoencapsulation improved its cytotoxic effect against C6 glioma cells and both compound forms attenuated the tumor development.