Nanoencapsulation of Olanzapine Increases Its Efficacy in Antipsychotic Treatment and Reduces Adverse Effects

Olanzapine is an atypical antipsychotic drug, whose chronic use has been associated with the development of potential adverse effects such as weight gain and cardio-metabolic disorders like hypercholesterolemia and diabetes. To circumvent these side effects, the controlled release of olanzapine is a promising approach to improve adhesion of schizophrenic patients to the treatment. An innovative strategy to prolong drug release consists of loading the drug into biodegradable polymeric lipid-core nanocapsules. In this study, particle size, polydispersity, pH, zeta potential and drug loading of olanzapine-loaded lipid-core nanocapsules were analyzed. Weight gain, biochemical parameters and antipsychotic activity were evaluated in male Wistar rats. The lipid-core nanocapsules had a mean diameter of 156 ± 13 nm, a polydispersity index lower than 0.1, a pH value of 6.12 ± 0.14, zeta potential of –17 ± 2.40 mV and encapsulation efficiency close to 100%. The animals treated with olanzapine-loaded lipid-core nanocapsules showed significantly lower weight gain (63.4 ± 19.6 g) and total cholesterol levels (66.2 ± 3.5 g · dl^–1), compared to those administered with free olanzapine (112.6 ± 10.3 g and 90.4 ± 2.4 g · dl^–1), respectively. Additionally, a more prolonged antipsychotic action was observed in the stereotyped behavior animal model induced by D, L-amphetamine, which affords to conclude that nanoencapsulation is a promising alternative to treat schizophrenic patients.