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Solid lipid nanoparticles (SLNs) were prepared by biocompatible and biodegradable solid-phase lipids. β-elemene is a safe natural essential oil with broad-spectrum anti-tumor activity. However, its clinical application has been adversely affected by its poor water solubility and limited bioavailability. SLN incorporation is a potential strategy to bypass the blood-brain barrier, the most important factor limiting the bioactivity of neurotherapeutics. The SLNs-β has the same efficacy as commercially available elemene in vitro and an enhanced brain drug accumulation in vivo. The survival rate data was promising and acute toxicity experiment proved its safety. All these data suggested that SLN-β is a safe and effective drug delivery system, especially for brain tumor therapy, and warrants further development. • Solid lipid nanoparticle is potential and espically for brain drug delivery system. • Solid lipid nanoparticle has the advantage of improving blood–brain barrier permeability of loaded drugs. • Different types of models were selected to test the ability of increasing drug accumulation in brain. • The solid lipid nanoparticle loaded with β-elemene which we prepared had a better performance. [ABSTRACT FROM AUTHOR]