Synergistic Combination of Doxorubicin and Paclitaxel Delivered by Blood Brain Barrier and Glioma Cells Dual Targeting Liposomes for Chemotherapy of Brain Glioma

Title:Synergistic Combination of Doxorubicin and Paclitaxel Delivered by Blood Brain Barrier and Glioma Cells Dual Targeting Liposomes for Chemotherapy of Brain Glioma

Volume: 17 Issue: 7

Author(s): Xiaoxiao Chen, Mingqing Yuan, Qianyu Zhang, Yu Ting Yang, Huile Gao and Qin He

Affiliation:

Keywords: Glioma, blood brain barrier, dual-ligand, combination therapy, liposomes, transferrin.

Abstract: Brain glioma has become a great threat to human health in decades. To maximize the therapeutic efficacy of brain glioma as well as minimize the side effects, drugs should be penetrated through the blood brain barrier (BBB) and then targeted to the brain carcinoma cells with effective concentration. A dual-ligand delivery strategy was employed to achieve both of these goals. Herein, both specific targeting ligand transferrin and cell-penetrating peptide TAT were conjugated onto liposomes (TF/TAT-LP) to develop a brain glioma dual-ligand delivery system. Synergistic combination of doxorubicin (DOX) and paclitaxel (PTX), compared with using them separately, could more efficiently suppress tumor aggravation. In vitro studies including cellular uptake and three-dimensional (3D) tumor spheroid penetration assays proved that TF/TAT-LP could target brain endothelial and carcinoma cells with deeply penetration through the endothelial monolayers and target to the core of the tumor spheroids. In vivo imaging proved that the TF/TAT-LP possesses the highest tumor distribution, which was also confirmed by fluorescent images of the brain section. Ultimately, the DOX and PTX-loaded TF/TAT-LP (TF/TAT-PTX/DOX-LP) shows the best anti-glioma effect with improvement of glioma bearing survival time. In conclusion, synergistic combination of doxorubicin and paclitaxel delivered by the TF/TAT-LP could efficiently target to the brain glioma with satisfying treatment efficiency, which may be a promising formulation for glioma therapy.

Cite this article as:

Chen Xiaoxiao, Yuan Mingqing, Zhang Qianyu, Ting Yang Yu, Gao Huile and He Qin, Synergistic Combination of Doxorubicin and Paclitaxel Delivered by Blood Brain Barrier and Glioma Cells Dual Targeting Liposomes for Chemotherapy of Brain Glioma, Current Pharmaceutical Biotechnology 2016; 17 (7) . https://dx.doi.org/10.2174/1389201017666160401144440