title: Nanoencapsulation Improves Relative Bioavailability and Antipsychotic Effect of Olanzapine in Rats.
abstract: 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.
authors: Frantiescoli A
authors: FA
authors: Dimer
authors: Maiara C
authors: MC
authors: Pigatto
authors: Camila A
authors: CA
authors: Boque
authors: Camila S
authors: CS
authors: Pase
authors: Katiane
authors: K
authors: Roversi
authors: Adriana R
authors: AR
authors: Pohlmann
authors: Marilise E
authors: ME
authors: Burger
authors: M K
authors: MK
authors: Rates
authors: Teresa
authors: T
authors: Dalla Costa
authors: Silvia S
authors: SS
authors: Guterres
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D001569:Benzodiazepines / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004058:Diffusion; D008657:Metabolic Clearance Rate; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D000077152:Olanzapine; D009928:Organ Specificity; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D012559:Schizophrenia / Q000188:drug therapy* / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D053769:Nanocapsules; D001569:Benzodiazepines; D000077152:Olanzapine