Efeito do tratamento com nanocápsulas poliméricas contendo clozapina sobre parâmetros de estresse oxidativo em ratos wistar

Abstract

Clozapine is a second-generation antipsychotic, of family dibenzodiazepine being treatment of first choice in refractory schizophrenia, owing outstanding effect about positive and negative symptoms disease. However, severe adverse effects limit their use in clinical therapy, such as agranulocytosis, hepatotoxicity and cardiotoxicity. In view these complications became necessary a pharmaceutical form able to vectorize the drug its site of action, reducing side effects and minimizing oxidative stress, making the nanosystems a promising tool for this purpose. The aim this study was to investigate the effect of treatment with nanosystems containing clozapine on oxidative stress parameters in Wistar rats. The study consisted of eight groups of male Wistar rats (n = 6) animals received the following treatments: saline solution (NaCl 0.9% 1.0 mL/Kg i.p.), free clozapine (25 mg/Kg i.p.), blank uncoated nanocápsulas (1.0 mL/Kg i.p.), clozapine-loaded uncoated nanocapsules (25 mg/Kg i.p.), blank chitosan-coated or polyethyleneglycol-coated nanocápsulas (1.0 mL/Kg i.p.), clozapine-loaded chitosan-coated or polyethyleneglycol-coated nanocapsules (25 mg/Kg i.p.). The animals received the formulation once a day for seven consecutive days and euthanized in the eighth day. It was collected global blood and organs heart, liver and kidney for further analysis. The nanosystems containing clozapine therapy was effective in maintaining blood levels within the normal range. Quantification of biochemical markers for cardiac, hepatic and renal function showed serum levels significantly decreased (p < 0.05) when compared free clozapine group, becoming more evident clinical improvement in the clozapine-loaded chitosan-coated nanocapsules group in the markers cardiac and hepatic. The histopathological analysis of the organs showed that the different nanosystems containing clozapine were able to reduce tissue damage. The activity of antioxidant enzymes catalase, superoxide dismutase and glutathione peroxidase were significantly higher in the groups with different nanosystems, such as the activity of reduced glutathione, being the clozapine-loaded chitosan-coated nanocapsules group the best results. How to oxidative damage in membrane lipids, plasma proteins and genetic material, the free clozapine induced damage while different nanosystems containing clozapine were able to reduce, being more evident in the clozapine-loaded polyethyleneglycol-coated nanocapsules. Thus, our findings suggest that different coatings can act in diverse and specific way for each organ or tissue through which possess higher affinity. The nanoencapsulation of clozapine is a promising therapeutic tool, able of mitigating the harmful effects of drug, minimizing oxidative stress, making a safer drug to patients.