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

Abstract

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.

Keywords:

• Chitosan
• ionic-gelation
• porcine-mucin
• schizophrenia
• stereotypy
• swimming normalization

Acknowledgements

The authors are grateful to Medopharma, Hosur, India, for gratis of risperidone and the management of Sree Vidyanikethan College of Pharmacy, Tirupati, India for rendering generous support to carry out the research work.

Disclosure statement

The authors declare that there are no conflicts of interest regarding the publication of this manuscript.