ArticleDrug delivery and translational research2026
Brain-targeted intranasal aripiprazole via modified chitosan nanoparticles: controlled release, pharmacokinetics, and pharmacodynamics.
Article in Drug delivery and translational research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Schizophrenia remains one of the most disabling mental disorders, and effective therapy is still limited by the difficulty of delivering drugs across the blood-brain barrier. Aripiprazole (Ari), a first-line atypical antipsychotic, exhibits restricted clinical performance due to poor solubility, extensive hepatic metabolism, and limited brain exposure. Herein, a novel intranasal nanocarrier system was developed to enable direct and sustained delivery of Ari to the brain. Chitosan nanoparticles (Cs-NPs) surface-modified with sodium dodecyl sulfate (SDS) were prepared by the ionic gelation method and optimized using a Box-Behnken design to evaluate the effects of SDS concentration, pH, and chitosan-to-tripolyphosphate ratio on particle size, zeta potential, and drug entrapment. The optimized formulation showed a mean particle size of ~ 200 nm, a positive surface charge, and an entrapment efficiency of 76.98 ± 7.6%. Transmission electron microscopy confirmed spherical morphology, while the in vitro release profile exhibited an initial burst followed by a sustained phase, indicating controlled-release behavior. Pharmacokinetic evaluation using LC-MS/MS revealed significantly enhanced Ari bioavailability and brain uptake following intranasal administration of the optimized Cs-NPs compared with oral, intravenous, and intranasal solutions. Pharmacodynamic testing in a ketamine-induced psychosis rat model (open-field and forced-swim tests) demonstrated improved antipsychotic efficacy. Neurochemical analysis showed restoration of dopamine and γ-aminobutyric acid levels, while histopathological findings confirmed structural improvement in hippocampal and cortical regions. Collectively, these results highlight the potential of modified Cs-NPs as a controlled-release, nose-to-brain delivery platform that enhances the therapeutic performance of Ari for the management of schizophrenia.
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