The Effect of Minor Doses of Olanzapine-Solid Lipid Nanoparticles on an Animal Model of Schizophrenia (Neurochemical and Behavioral Study) and the Side Effect

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.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.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.