Preparation of multifunctional targeting epirubicin liposomes and their efficacy in inhibiting brain glioma cells / 中国药学杂志

ABSTRACT

OBJECTIVE: To develop a kind of multifunctional targeting epirubicin liposomes for the treatment of brain tumor, to characterize their physicochemical properties, and to observe their targeting effects on the brain microvascular endothelial cells (BM-VECs) and on the brain glioma cells. METHODS: The 2-amino-2-deoxy-β-Z)-glucopyranose(NH2-Glu) was used as a targeting molecule and conjugated with a cholesterol-polyethylene glycol derivative (Chol-PEG2000-NHS) for obtaining the targeting functional material aimed at targeting to glucose transporter-1 (Glut-1) on the BMVECs of blood-brain barrier and further targeting to the glioma cells. To prepare the multifunctional targeting epirubicin liposomes, the targeting functional material was modified onto the surface of liposomes, and epirubicin was loaded into the core of liposomes as the anticancer drug. The encapsulation efficiency, particle size, polydispersity indexes and Zeta potential of the liposomes were measured, their cellular uptakes were performed on the BMVECs and the glioma cells. The inhibitory effect was performed on the glioma cells. RESULTS: The analysis by MALDI-TOF-MS demonstrated that the targeting functional material, Chol-PEG2000-Glu, was successfully synthesized. The multifunctional targeting epirubicin liposomes were prepared, and had an average particle size of approximately 125 nm, and were negatively charged. The encapsulation efficiency of epirubicin in the liposomes was about 93%. Results from flow cytometry indicated that the multifunctional targeting epirubicin liposomes had the highest cellular uptakes by BMVECs and by two kinds of brain glioma cells as compared with no-targeting epirubicin liposomes. The cytotoxic study showed that the multifunctional targeting epirubicin liposomes had the strongest inhibitory effect to brain glioma cells as compared with free epirubicin or no-targeting epirubicin liposomes. CONCLUSION: A new targeting material (Chol-PEG2000-Glu) and the multifunctional targeting epirubicin liposomes are developed, and the multifunctional targeting epirubicin liposomes exhibit the potential lortransporting across the blood-brain barrier (BBB), and selectively inhibiting the brain glioma cells.