title: Haloperidol-loaded polysorbate-coated polymeric nanocapsules increase its efficacy in the antipsychotic treatment in rats.
abstract: 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 (0.2mg/kg ip) and four doses of D,L-amphetamine, AMPH (8.0mg/kg ip), injected every 3h (0, 3, 6 and 9h). 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 1h after a single dose of H-NC or its free solution (0.2mg/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 (0.2mg/kg ip) for 28 days showed a lower incidence of extrapyramidal effects than those treated with the free drug (0.2mg/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.
authors.affiliation: Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria-UFSM, Santa Maria-RS, Brazil. dalilabenvegnu@yahoo.com.br
authors.forename: Dalila M
authors.initials: DM
authors.lastname: Benvegnú
authors.forename: Raquel C S
authors.initials: RC
authors.lastname: Barcelos
authors.forename: Nardeli
authors.initials: N
authors.lastname: Boufleur
authors.forename: Patrícia
authors.initials: P
authors.lastname: Reckziegel
authors.forename: Camila S
authors.initials: CS
authors.lastname: Pase
authors.forename: Aline F
authors.initials: AF
authors.lastname: Ourique
authors.forename: Ruy Carlos R
authors.initials: RC
authors.lastname: Beck
authors.forename: Marilise E
authors.initials: ME
authors.lastname: Bürger
mesh_terms: D000661:Amphetamine; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use* / Q000633:toxicity*; D055598:Chemical Phenomena; D004195:Disease Models, Animal; D004409:Dyskinesia, Drug-Induced / Q000209:etiology*; D006220:Haloperidol / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use* / Q000633:toxicity*; D008297:Male; D053769:Nanocapsules; D011136:Polysorbates; D051381:Rats; D017208:Rats, Wistar; D012559:Schizophrenia / Q000188:drug therapy; D013239:Stereotyped Behavior / Q000187:drug effects*
chemical_list: D014150:Antipsychotic Agents; D053769:Nanocapsules; D011136:Polysorbates; D000661:Amphetamine; D006220:Haloperidol