Nanoparticle formulation improves the anticonvulsant effect of clonazepam on the pentylenetetrazole-induced seizures: behavior and electroencephalogram

Article Article scientifique Article Nanoparticle formulation improves the anticonvulsant effect of clonazepam on the pentylenetetrazole-induced seizures: behavior and electroencephalogram eng 2014 author Leyva-Gómez Gerardo author González-Trujano María Eva author López-Ruiz Edith author Couraud Pierre-Olivier author Wekslerg Babette author Romero Ignacio author Miller Florence 717239 author Delie Salmon Florence 121330 author Allémann Eric 0000-0002-6598-9521 26730 author Quintanar-Guerrero David 2509-2519 10.1002/jps.24044 24916334 0022-3549 To document the efficacy of clonazepam (CLZ) either free as a solution or loaded in solid lipid nanoparticles (CLZ-SLN) or mixed micelles (CLZ-MM), the in vitro blood-brain barrier permeability of the formulations was determined. Behavior and/or electroencephalograms (EEGs) of rodents receiving treatments were also studied. The in vitro permeability of CLZ increased when associated with SLN, but decreased in the case of MM. The occurrence of the pentylenetetrazole (PTZ)-induced seizures in mice was significantly prevented by CLZ, even when exposed a lower dose of CLZ-SLN after administration by the oral route. The behavioral severity and EEGs showing the PTZ-induced paroxystic activity in rats diminished significantly in the presence of CLZ alone (0.3 mg/kg), and were almost totally prevented in the rats treated with CLZ-SLN (equivalent to 0.3 mg/kg). The frequency, duration, and spreading of the spikes-wave of rats treated with CLZ-SLN decreased significantly as compared with CLZ alone, CLZ-MM, or the vehicle. These results show an in vitro-in vivo correlation in the enhanced blood-brain barrier permeability of SLN formulation, and a contribution of MM to the carrier effect of drugs toward the bloodstream and brain, where this pharmaceutical formulation of CLZ-SLN improves the anticonvulsant effect of this benzodiazepine, thus offering additional advantages after oral administration. Animals Anticonvulsants/administration & dosage/therapeutic use Cell Line Clonazepam/administration & dosage/therapeutic use Drug Carriers/chemistry Electroencephalography Humans Lipids/chemistry Male Mice Micelles Nanoparticles/chemistry Pentylenetetrazole Rats Rats, Wistar Seizures/chemically induced/drug therapy Dewey 615 31 Section des sciences pharmaceutiques 17 false 883 Technologie pharmaceutique Journal of Pharmaceutical Sciences 103 8 ee60672d-26f0-46e1-946b-715a067d901b Article (Published version) Restricted Leyva-Gomez_JPS_2014.pdf 4567401 application/pdf restrictedAccess Faculté des sciences / Section des sciences pharmaceutiques

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Nanoparticle formulation improves the anticonvulsant effect of clonazepam on the pentylenetetrazole-induced seizures: behavior and electroencephalogram	Journal of Pharmaceutical Sciences			2014	537	1

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