Haloperidol-loaded polysorbate-coated polymeric nanocapsules increase its efficacy in the antipsychotic treatment in rats

Haloperidol is an antipsychotic drug associated with the development of movement disorders. We evaluated the effect of its nanoencapsulation on its pharmacological activity and motor side effects. Haloperidol-loaded polysorbate-coated nanocapsules (H-NC) showed nanometric size, negative zeta potential and low polydispersity indices and high encapsulation efficiency (>95%). Rats received a single dose of H-NC (0.2 mg/kg ip) and four doses of D,L-amphetamine, AMPH (8.0 mg/kg ip), injected every 3 h (0, 3, 6 and 9 h). The AMPH-induced stereotyped movements were quantified in the intervals of 15 min after each of four doses of AMPH, demonstrating greater pharmacological efficacy of the H-NC over free haloperidol (FH). The acute motor side effects were evaluated 1 h after a single dose of H-NC or its free solution (0.2 mg/kg ip). The group treated with H-NC presented lower extrapyramidal effects (catalepsy and oral dyskinesia) than those treated with FH. In the last experimental set, rats sub-chronically treated with a daily dose of H-NC (0.2 mg/kg ip) for 28 days showed a lower incidence of extrapyramidal effects than those treated with the free drug (0.2 mg/kg ip). Our findings showed the potential of using H-NC in the development of a nanomedicine aimed at increasing the efficacy of this antipsychotic drug and reducing its side effects. (C) 2010 Elsevier B.V. All rights reserved.