Haloperidol-loaded polysorbate-coated polymeric nanocapsules decrease its adverse motor side effects and oxidative stress markers in rats

Haloperidol is the most widely used antipsychotic drug in the treatment of psychiatric disorders. Despite its satisfactory therapeutic effect, its chronic use is related to severe motor side effects. Here, we investigate the incidence of motor side effects of haloperidol-loaded nanocapsules when compared to free haloperidol and the relation with oxidative stress (OS) development. Both vehicle (B-NcFO) and haloperidol loaded polysorbate-coated nanocapsules suspension (H-NcFO) prepared with fish oil as core showed uniform and rounded particles, nanometric size, negative zeta potential, low polydispersity indices and high encapsulation efficiency. Wistar rats received a single dose of free haloperidol (FH), B-NcFO or H-NcFO (0.2 mg/kg ip) and were submitted to acute motor side effects evaluation 1 h after the injection. Lower catalepsy time and oral dyskinesia were observed in H-NcFO-treated group than in FH group; however, both formulations decreased animals' locomotor activity. In a experiment performed subchronically, rats injected daily with H-NcFO (0.2 mg/kg-ip) for 28 days showed decreased oral dyskinesia frequency and catalepsy time and no impairment on locomotor activity as compared to FH group (0.2 mg/kg-ip). FH group showed higher OS, as observed by increased lipid peroxidation and reduced glutathione levels and catalase activity in extrapyramidal region. Our findings showed that nanocapsules may be an efficient form to prevent or minimize haloperidol motor side effects, which are related to OS development, ameliorating psychiatric patients' quality of life.