Nanoencapsulation Improves Relative Bioavailability and Antipsychotic Effect of Olanzapine in Rats.

This study aimed to investigate the pharmacokinetics, tissue distribution and antipsychotic activity of olanzapine administered as free drug (OLA-FREE) or loaded into lipid-core nanocapsules (OLA-LNC). OLA-LNC were successfully developed with a particle size of 142 ± 4 nm and a zeta potential of -19.6 ± 0.6 mV. Pharmacokinetics and tissue distribution studies were carried out after the administration of free and nanoencapsulated olanzapine (10 mg/kg) by intraperitoneal route to male Wistar rats. Higher olanzapine concentrations and AUC(0-12 h) were found in plasma and tissues evaluated after the administration of OLA-LNC compared to the drug in the free form, resulting in a relative bioavailability of 226.7% in the plasma. As a result olanzapine loaded lipid-core nanocapsules presented pronounced and long-lasting effects on central nervous system. These nanocapsules (10 mg/kg, i.p.) significantly diminished the stereotyped behavior induced by D,L-amphetamine up to 12 hours whereas olanzapine free-form (10 mg/kg, i.p.) was effective during 03 hours only. Moreover, olanzapine loaded lipid-core nanocapsules (1.0 mg/kg, i.p.) have shown a marked sedative effect and also prevented the prepulse inhibition disruption induced by apomorphine at lower dose than olanzapine in free-form (2.5 mg/kg, i.p.). Herewith, we point to the nanoencapsulation as a strategy for reducing the concentration of olanzapine in pharmaceutical formulations.