Acute toxicity and anticonvulsant activity of liposomes containing nimodipine on pilocarpine-induced seizures in mice

NEUROSCIENCE LETTERS

卷:585

Article

Gayoso e Almendra Ibiapina Moreno, Lina Clara^1,2  Ferro Cavalcanti, Isabella Macario²  Satyal, Prabodh³  Santos-Magalhaes, Nereide Stela²  Lins Rolim, Hercilia Maria¹  Freitas, Rivelilson Mendes¹ 

[1] Univ Fed Piaui, Lab Expt Neurochem Res, Teresina, PI, Brazil

[2] Univ Fed Pernambuco, Immunopathol Keizo Asami Lab, Recife, PE, Brazil

[3] Univ Alabama, Dept Chem, Huntsville, AL 35899 USA

关键词: Anticonvulsant;    Liposomes;    Mice;    Nimodipine;    Toxicity;   

DOI  :  10.1016/j.neulet.2014.11.025

来源: Elsevier

【 摘 要 】

Nimodipine has been shown to have an inhibitory action on seizures and brain damage in rodents. However, the pharmaceutical applicability of this drug is limited by its low solubility in gastrointestinal fluids and high first-pass effect in the liver, which leads to low bioavailability. These difficulties can be overcome through the use of liposomes. The aim of the present study is to evaluate the toxicity and anticonvulsant activity of liposomes containing nimodipine (NMD-Lipo) on pilocarpine-induced seizures. NMD-Lipo was prepared using the lipid-film hydration method. Central nervous system toxicity of NMD-Lipo was assessed by Hippocratic screening. Systemic toxicity was evaluated by analyses of biochemical and hematological parameters and by observing possible signs of toxicity. The possible anticonvulsant activity was tested by the pilocarpine model. The administration of the NMD-Lipo at doses of 0.1, 1, and 10 mg/kg caused no toxicity in animals. Furthermore, NMD-Lipo prevented the installation of 100% of the pilocarpine-induced seizures and prevented the death of 100% of the mice treated with pilocarpine. These data shown that NMD-Lipo has an anticonvulsant activity significantly superior to free NMD, suggesting that the liposomes promoted a drug controlled release by improving its bioavailability and consequently increasing its pharmacological activity. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

【 授权许可】

Free