Background and Objective: Olanzapine (OLZ) is an atypical psychotic agent; the poor bioavailability of olanzapine is the most issue in its treatment. The present work was carried out to evaluate the oral form of olanzapine solid lipid nanoparticles (OLZ-SLN) to overcome to its poor bioavailability and compare between the effect of different doses of OLZ and OLZ-SLN on ketamine-induced schizophrenic-like symptoms. The study extended to evaluate the adverse effects of sub-chronic administration of these doses of OLZ and its SLN.
Methods: OLZ-SLN was prepared by hot homogenization, particle size, zeta potential, in vitro release and entrapping efficiency studies were performed. To assess the effective dose in treatment of schizophrenia, the effect of different doses of OLZ and OLZ-SLN on open field and passive avoidance tests were carried out. Excitatory and inhibitory amino acids, as well as dopamine and serotonin in brain regions, and BCL2 were performed. Liver function, lipid profile and lipid peroxide, and then assessed to evaluate the side effect.
The Results and Conclusion: The new oral formula showed high stability and sustained release. The administrated of low and high dose of OLZ-SLN that equivalent to (1/10 and 1/20 from the therapeutic dose) before ketamine attenuated the behavioral abnormalities by blocking the effect of ketamine-induced increased in glutamate, dopamine and serotonin levels and enhanced apoptosis in the studied brain areas. In addition, the sub-chronic treatment with OLZ-SLN showed no adverse effect while the treatment with OLZ free form did.