Formulation and biopharmaceutical evaluation of risperidone-loaded chitosan nanoparticles for intranasal delivery

Objective: High lipophilicity and extensive hepatic metabolism limits the oral application of risperidone in the treatment of CNS disorders. In order address this limitation, risperidone (RS) loaded chitosan nanoparticles (CS-NPs) were processed for intranasal administration in the management of schizophrenia. Methods: RS loaded CS-NPs were prepared by ionic gelation of chitosan with tripolyphosphate and stabilized by tween 80/ poloxamer 188. The CS-NPs were characterized by FTIR, DSC, particle size, zeta potential and surface morphology. Entrapment efficiency, mucoadhesive strength, in vitro drug release, and release kinetics of CS-NPs were evaluated. Pharmacokinetics and pharmacodynamics of RS loaded CS-NPs were studied using Wistar rats. Stereotypy behavior and swimming normalization tests were conducted in amphetamine induced psychosis in animals. Results: Risperidone nanoparticles (RP12) were produced with an average size of 86 nm, polydispersity index of 0.287, zeta potential of +36.6 mV, mucoadhesion of 68.9% and entrapment efficiency of 77.96%. CS-NPs released the RS in controlled manner with Fickian diffusion mode. Maximum concentration of RS in plasma was 1240 ng/ml at 4 h for RP12, and 403.8 ng/ml at 2 h for RS sample. RS loaded CS-NPs significantly reduced the stereotypy score in experimental animals that indicated the efficiency of CS-NPs in delivery of RS at brain tissues and moreover amphetamine effect was reversed. Thus, RS loaded CS-NPs proved as potential delivery systems against induced psychotic disorders. Conclusion: Risperidone loaded chitosan nanoparticles were effective against schizophrenia via intranasal route.