title: Acute toxicity and anticonvulsant activity of liposomes containing nimodipine on pilocarpine-induced seizures in mice.
abstract: 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.
authors.affiliation: Laboratory of Experimental Neurochemistry Research, Federal University of Piaui, Teresina, PI, Brazil; Immunopathology Keizo-Asami Laboratory, Federal University of Pernambuco, Recife, PE, Brazil.
authors.forename: Lina Clara Gayoso e Almendra Ibiapina
authors.initials: LC
authors.lastname: Moreno
authors.affiliation: Immunopathology Keizo-Asami Laboratory, Federal University of Pernambuco, Recife, PE, Brazil.
authors.forename: Isabella Macário Ferro
authors.initials: IM
authors.lastname: Cavalcanti
authors.affiliation: Chemistry Department, University of Alabama in Huntsville, AL 35899, USA.
authors.forename: Prabodh
authors.initials: P
authors.lastname: Satyal
authors.affiliation: Immunopathology Keizo-Asami Laboratory, Federal University of Pernambuco, Recife, PE, Brazil.
authors.forename: Nereide Stela
authors.initials: NS
authors.lastname: Santos-Magalhães
authors.affiliation: Laboratory of Experimental Neurochemistry Research, Federal University of Piaui, Teresina, PI, Brazil.
authors.forename: Hercília Maria Lins
authors.initials: HM
authors.lastname: Rolim
authors.affiliation: Laboratory of Experimental Neurochemistry Research, Federal University of Piaui, Teresina, PI, Brazil. Electronic address: rmendesfreitas@hotmail.com.
authors.forename: Rivelilson Mendes
authors.initials: RM
authors.lastname: Freitas
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D008081:Liposomes; D008297:Male; D051379:Mice; D009553:Nimodipine / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D010862:Pilocarpine; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D013239:Stereotyped Behavior / Q000187:drug effects; D023382:Toxicity Tests, Acute
chemical_list: D000927:Anticonvulsants; D008081:Liposomes; D010862:Pilocarpine; D009553:Nimodipine
keywords: Anticonvulsant; Liposomes; Mice; Nimodipine; Toxicity