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Olanzapine (OZ) is atypical antipsychotic drug that suffers from low brain permeability due to efflux by P-glycoproteins and hepatic first-pass metabolism. The current work aimed to develop OZ-loaded micellar nanocarriers and investigate their nose-to-brain targeting potential. OZ-loaded (5 mg/ml) micelles (F1–F12) were prepared, using a Pluronic® mixture of L121 and P123, adopting thin-film hydration method. The micelles were evaluated for turbidity, particle size, morphology, drug-entrapment efficiency (EE%), drug-loading characteristics, in vitro drug release and ex vivo nasal toxicity in sheep. The in vivo biodistribution and pharmacokinetic studies in the brain/blood following intravenous (i.v.) and intranasal (i.n.) administrations of technetium-labeled OZ-loaded micelles and OZ-solution were evaluated in rats. Spherical micelles ranging in size from 18.97 to 380.70 nm were successfully developed. 1H NMR studies confirmed OZ incorporation into micelle core. At a drug:Pluronic® L121:Pluronic® P123 ratio of 1:8:32 (F11), the micelles achieved a conciliation between kinetic and thermodynamic stability, high drug-EE%, controlled drug-release characteristics and evoked minor histopathological changes in sheep nasal mucosa. The significantly (P < 0.05) higher values for F11 micelles (i.n.); brain/blood ratio (0.92), drug targeting index (5.20), drug targeting efficiency (520.26%) and direct transport percentage (80.76%) confirm the development of a promising non-invasive OZ-loaded nose-to-brain delivery system.