Preparation and in vitro Evaluation of Clozapine Chitosan Nanoparticles for Intranasal Administration

Clozapine is widely used to treat schizophrenia, but it has low oral bioavailability (<27%), degradation in GI environment, and high hepatic first-pass metabolism. The present research work aimed to overcome these issues by designing tailored clozapine loaded nanoparticles (NPs) and to deliver them to the brain via the intranasal pathway, to enhance brain targeting of antipsychotic drugs. Chitosan–sodium tri polyphosphate and chitosan– sodium alginate NPs loaded with Clozapine (CZ) were prepared by using ionotropic gelation and ionotropic pregelation methods. SEM showed spherical-shaped NPs, while the average dynamic size was measured by dynamic light scattering. Optimized clozapine loaded nanoparticles (C2,C7) showed 56% and 55% encapsulation efficiency, respectively, with particle sizes of (453 - 425)nm. The in vitro drug release from formulas exhibited sustained release of clozapine, were 69.2% and 98.7% respectively, within 24h. The release profile was characterized by an initial fast release in phosphate buffer, followed by a continuous release phase; the drug release mechanism from polymers was in correspondence with Fickian diffusion. CZ-loaded NPs are a promising strategy for managing schizophrenia. Nose-to-brain pathway enhances safety and patient compliance of CZ.