Preparation of Multifunctional Paclitaxel Liposomes for Treatment of Brain Glioma

Abstract

Invasive brain glioma is the most lethal type of cancer with highly infiltrating nature. It leads to an extremely poor prognosis and makes complete surgical removal of the tumor virtually impossible. Paclitaxel shows antitumor activities against invasive gliomas. However, the efficacy of paclitaxel against gliomas is limited by its poor solubility, non-penetration across the blood-brain barrier (BBB), and the resistance of brain glioma cells. A single medication cannot obtain optimal efficacy, while a combinational drug therapy may overcome this issue. This report focuses on liposomal formulations by incorporating paclitaxel and artemether and describes the preparation and characterizations of multifunctional paclitaxel liposomes, which are designed to treat brain glioma along with eliminating the cancer stem cells. In this liposomal drug delivery system, paclitaxel is used as the anticancer drug and artemether is used as the regulator; two functional materials (MAN-TPGS₁₀₀₀ and DQA-PEG₂₀₀₀-DSPE) are synthesized and used as functional materials by modifying onto the surface of the liposomes; egg phosphatidylcholine (EPC) and cholesterol are used as liposomal materials. The multifunctional paclitaxel liposomes, prepared by thin-film hydration, are about 80 nm, nearly electrically neutral and round with relatively smooth surfaces. The encapsulation efficiencies of paclitaxel or artemether are >80%. The multifunctional paclitaxel liposomes exhibit long circulation time, strong ability of transporting across BBB, and strong inhibitory effect in the brain glioma-bearing rats.