Nose-to-brain delivery of simvastatin mediated by chitosan-coated lipid-core nanocapsules allows for the treatment of glioblastoma in vivo

[Display omitted] •Production of chitosan-coated lipid-core nanocapsules containing simvastatin (LNCSVT-chit) is proposed for nose-to-brain delivery.•LNCSVT-chit demonstrated to be cytotoxic in two glioma cell lines.•Nanoencapsulation improves the amount of simvastatin into rat brain after nasal administration.•LNCSVT-chit treatment decreased the tumor size and malignancy in glioblastoma-bearing rats. Glioblastoma is the most common and lethal malignant brain tumor. Despite simvastatin (SVT) showing potential anticancer properties, its antitumoral effect against glioblastoma appears limited when the conventional oral administration route is selected. As a consequence, nose-to-brain delivery has been proposed as an alternative route to deliver SVT into the brain. This study aimed to prepare chitosan-coated simvastatin-loaded lipid-core nanocapsules (LNCSVT-chit) suitable for nose-to-brain delivery and capable of fostering antitumor effects against glioblastoma both in vitro and in vivo. Results showed that the nanocapsules present adequate particle size (mean diameter below 200 nm), narrow particle size distribution (PDI