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This study aims to develop, characterize, and examine olanzapine-loaded solid lipid nanocarriers (OLAN-SLNs) for effective brain delivery. OLAN has poor water solubility and low penetration through blood–brain barrier (BBB). Herein, OLAN-SLNs were fabricated using high-pressure homogenization (HPH) method followed by their investigation for particle properties. Moreover,  in vitro  release and  in vivo  pharmacokinetics profiles of OLAN-SLNs were compared with pure drug. Anti-psychotic activity was performed in LPS-induced psychosis mice model. Furthermore, expressions of the COX-2 and NF-κB were measured trailed by histopathological examination. The optimized formulation demonstrated nanoparticle size (149.1 nm) with rounded morphology, negative zeta potential (–28.9 mV), lower PDI (0.334), and excellent entrapment efficiency (95%). OLAN-SLNs significantly retarded the drug release and showed sustained release pattern as compared to OLAN suspension. Significantly enhanced bioavailability (ninefold) was demonstrated in OLAN-SLNs when compared with OLAN suspension. Behavioral tests showed significantly less immobility and more struggling time in OLAN-SLNs treated mice group. Additionally, reduced expression of COX-2 and -NF κB in brain was found. Altogether, it can be concluded that SLNs have the potential to deliver active pharmaceutical ingredients to brain, most importantly to enhance their bioavailability and antipsychotic effect, as indicated for OLAN in this study.

Improved biopharmaceutical performance of antipsychotic drug using lipid nanoparticles via intraperitoneal route