Background: The present work was designed to explore the efficacy of neuroactive drug
(risperidone) loaded chitosan lipid nanoparticle (RIS-CH-LNPs) to enhance the bioactivity in schizophrenia
via the nasal route.
Methods: The three-factor and three-level formulation by design approach was used for optimization
and their effects were observed on (Y1) size in nm, (Y2) % drug loading, and (Y3) % drug release. The
optimized formulation RIS-CH-LNPopt was further evaluated for its surface morphology, ex-vivo permeation
study, in-vivo behavior study, and stability study. The developed RIS-CH-LNPs showed
nanometric size range with high drug loading and prolonged drug release.
Results: The optimized formulation (RIS-CH-LNPopt) has shown the particle size (132.7 nm), drug
loading (7.6 %), drug release (80.7 %) and further ex-vivo permeation study showed 2.32 fold enhancement
over RIS-SUS(suspension). In-vivo behavior studies showed that RIS-CH-LNPopt is able to show
significant greater bioefficacy as compared to RIS-SUS [intranasal (i.n), intravenous (i.v)]. The pharmacokinetic
and brain/plasma ratio of developed chitosan nanoparticle was higher at all time-points as
compared to RIS-SUS either given by intranasal or intravenous route that proves the direct nose to brain
transport pathway of the drug via nasal administration. The developed chitosan nanoparticle increases
nose to brain drug delivery as compared to the dispersion of equivalent dose.
Conclusion: The findings of this study substantiate the existence of a direct nose-to-brain delivery route