Nanoparticle Formulation Improves the Anticonvulsant Effect of Clonazepam on the Pentylenetetrazole-Induced Seizures: Behavior and Electroencephalogram
Por:
Leyva-Gõmez G., González-Trujano M.E., Lopez-Ruiz, E, Couraud, PO, Wekslerg B., Romero I., Miller F., Delie F., Allémann E., Quintanar-Guerrero D.
Publicada:
1 ago 2014
Categoría:
Pharmaceutical Science
Resumen:
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. (c) 2014 Wiley Periodicals, Inc. and the American
Pharmacists Association J Pharm Sci 103:2509-2519, 2014
Filiaciones:
Leyva-Gõmez G.:
Univ Nacl Autonoma Mexico, Facultad Estudios Super Cuautitlan, Lab Invest & Posgrad Tecnol Farmaceut, Mexico City 54740, Estado De Mexic, Mexico
González-Trujano M.E.:
Direcciõn de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramõn de la Fuente Muñiz, México, D.F., Mexico
Wekslerg B.:
Division of Hematology and Oncology, Weill Cornell Medical College, New York, NY 10065, United States
Romero I.:
Department of Life Sciences, Faculty of Science, Open University, Milton Keynes, United Kingdom
Miller F.:
Unité U1002 INSERM, Faculté de Médecine, Université Paris Descartes Paris, Sorbonne Paris Cité, France
Section des Sciences Pharmaceutiques, Technologie Pharmaceutique, Université de Genève, Geneva 41211, Switzerland
Delie F.:
Section des Sciences Pharmaceutiques, Technologie Pharmaceutique, Université de Genève, Geneva 41211, Switzerland
Allémann E.:
Section des Sciences Pharmaceutiques, Technologie Pharmaceutique, Université de Genève, Geneva 41211, Switzerland
Quintanar-Guerrero D.:
Univ Nacl Autonoma Mexico, Facultad Estudios Super Cuautitlan, Lab Invest & Posgrad Tecnol Farmaceut, Mexico City 54740, Estado De Mexic, Mexico
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