Chitosan-coated nanocapsules ameliorates the effect of olanzapine in prepulse inhibition of startle response (PPI) in rats following oral administration

In this study, olanzapine-loaded lipid-core nanocapsules were successfully developed and coated with two different chitosan solutions (same concentration of chitosan but either in 1% acetic acid solution or in acetate buffer pH 5.5) aiming to increase the mucoadhesion and the brain delivery of olanzapine in order to improve the antipsychotic effect after oral administration. These nanoformulations underwent a full physicochemical characterization followed by efficacy evaluation in PPI in rats. The formulation selected for the PPI study (nanocapsules coated with chitosan solution in sodium acetate buffer pH 5.5, NCOLA-B) showed pH of 5.9 +/- 0.2, diameter of 162 +/- 12 nm with polydispersity index of 0.24 +/- 0.01, zeta potential of +6.9 +/- 0.7 mV, drug content of 1.06 mg.mL(-1) with 42.2% of encapsulation efficiency. Moreover, the nanocapsules showed spherical shape by transmission electron microscopy, suitable physical stability by multiple light scattering, control of drug release (dialysis bag method), low viscosity with Newtonian behavior and great mucin adhesion capacity. Unlike olanzapine solution (10 mg.mL(-1)), NCOLA-B (1 mg.mL(-1)) prevented the PPI disruption induced by apomorphine (4 mg.kg(-1), s.c.) when administered by the oral route. In conclusion, these findings open new possibilities for the nanoformulation composed of nanocapsules coated with chitosan as a novel strategy for olanzapine delivery.