To improve its poor aqueous solubility and stability, the potential chemopreventive agent quercetin was encapsulated in freeze-dried polymeric micelles by a thin film hydration and vacuum freeze-drying process before being used for glioma chemotherapy. The micelle characteristics, release profile, cellular uptake, intracellular drug concentration, transport across the blood-brain barrier, and antitumor efficiency in vivo were investigated. Results showed that the particle size of quercetin-loaded freeze-dried nanomicelles (QUE-FD-NMs) ranged from 20 to 80 nm, with an efficiently sustained release profile. Increased intracellular uptake into Caco-2 cells with low cytotoxicity, efficient penetration of BBB, and powerful cytotoxicity on C6 glioma cells were observed. QUE-FD-NMs accumulated in tumor-bearing brain tissues and exhibited significant antitumor effects in vivo, which significantly benefited the survival of glioma-bearing mice. These findings suggest that freeze-drying micelles loaded with quercetin is a promising drug delivery method for glioma therapy.Graphical abstract
A novel drug delivery system for the treatment of glioma was developed. Quercetin-loaded freeze-dried nanomicelles (QUE-FD-NMs) significantly increased cellular uptake of quercetin into Caco-2 cells with low cytotoxicity, effective penetration of the blood-brain barrier, and powerful cytotoxicity on C6 glioma cells. Furthermore, QUE-FD-NMs exhibited significant anti-tumor effects in vivo, providing significant survival benefit. Therefore, freeze-dried nanomicelles loaded with quercetin are a promising drug delivery system for targeting brain tumors, particularly glioma.