Title:The Effect of Minor Doses of Olanzapine-Solid Lipid Nanoparticles on an Animal Model of Schizophrenia (Neurochemical and Behavioral Study) and the Side Effect
Volume: 9
Issue: 4
Author(s): Areeg Abd-Elrazek*Tayseer Elnawawy
Affiliation:
- Department of Physiology, National Organization for Drug Control and Research (NODCAR), Giza,Egypt
Keywords:
Solid lipid nanoparticles, antipsychotic drugs, hepatotoxicity, excitatory and inhibitory amino acids, monoamines,
open field test, passive avoidance test.
Abstract: Background and Objective: Olanzapine (OLZ) is an atypical psychotic agent; the poor
bioavailability of olanzapine is the most important issue in its treatment. The present work was carried
out to evaluate the oral form of olanzapine solid lipid nanoparticles (OLZ-SLN) to overcome its poor
bioavailability and compare between the effect of different doses of OLZ and OLZ-SLN on ketamineinduced
schizophrenic-like symptoms. The study was extended to evaluate the adverse effects of subchronic
administration of these doses of OLZ and its SLN.
Methods: OLZ-SLN was prepared by hot homogenization, particle size, zeta potential and in vitro
release and entrapping efficiency studies were performed. In order to assess the effective dose in the
treatment of schizophrenia, the effect of different doses of OLZ and OLZ-SLN on open field was
assessed and passive avoidance tests were carried out. The test was performed to examine the effects
of excitatory and inhibitory amino acids, as well as dopamine and serotonin levels in the brain
regions.
Results and Conclusion: The new oral formula showed high stability and sustained release. The administration
of low and high dose of OLZ-SLN equivalent to (1/10 and 1/20 from the therapeutic dose
before ketamine attenuated the behavioral abnormalities by blocking the effect of ketamine-induced increase
in glutamate, dopamine and serotonin levels and enhanced apoptosis were studied in the brain
areas. In addition, the sub-chronic treatment with OLZ-SLN showed no adverse effect while the treatment
with OLZ free form did.
