Dual-targeting nanocarrier based on glucose and folic acid functionalized pluronic P105 polymeric micelles for enhanced brain distribution

Chemotherapeutics cannot effectively reach brain glioma due to the blood-brain barrier (BBB) and blood-brain tumour barrier (BBTB). To overcome these obstacles, dual-targeting DOX micelles (GF-DOX) were developed to deliver the drug across the BBB and reach the tumour site. In this study, we investigated the BBB targeting ability and the brain delivery of GF-DOX in mice. Results showed that the cellular uptake by brain microvascular endothelial cells (BMVECs) of GF-DOX was significantly higher than that by P105-DOX through caveolae- and clathrin-mediated endocytosis. An in vivo pharmacokinetic study in rats indicated that GF-DOX significantly increased the bioavailability of DOX (4.6-fold), as opposed to the control solution. The distribution of preparations in mice showed that GF-DOX could significantly increase the amount of DOX in the brain (P < 0.05). The survival time of tumour-bearing mice of the GF-DOX group (32 days) was significantly longer than that of the free DOX group (19 days, P = 0.024), or other controls due to the dual-targeting effect of GF-DOX. In conclusion, the dual-targeting GF-DOX could improve the efficacy of anti-tumour drugs in the treatment of brain glioma in vitro and in vivo.