Journal of Controlled Release 2010-01-25

Dual-targeting daunorubicin liposomes improve the therapeutic efficacy of brain glioma in animals.

Xue Ying, He Wen, Wan-Liang Lu, Ju Du, Jia Guo, Wei Tian, Ying Men, Yan Zhang, Ruo-Jing Li, Ting-Yuan Yang, De-Wei Shang, Jin-Ning Lou, Liang-Ren Zhang, Qiang Zhang

Index: J. Control. Release 141(2) , 183-92, (2010)

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Abstract

Chemotherapy for brain glioma has been of limited value due to the inability of transport of drug across the blood-brain barrier (BBB) and poor penetration of drug into the tumor. For overcoming these hurdles, the dual-targeting daunorubicin liposomes were developed by conjugating with p-aminophenyl-alpha-D-manno-pyranoside (MAN) and transferrin (TF) for transporting drug across the BBB and then targeting brain glioma. The dual-targeting effects were evaluated on the BBB model in vitro, C6 glioma cells in vitro, avascular C6 glioma tumor spheroids in vitro, and C6 glioma-bearing rats in vivo, respectively. After applying dual-targeting daunorubicin liposomes, the transport ratio across the BBB model was significantly increased up to 24.9%. The most significant uptake by C6 glioma was evidenced by flow cytometry and confocal microscope. The C6 glioma spheroid volume ratio was significantly lowered to 54.7%. The inhibitory rate to C6 glioma cells after crossing the BBB was significantly enhanced up to 64.0%. The median survival time of tumor bearing rats after administering dual-targeting daunorubicin liposomes (22 days) was significantly longer than that after giving free daunorubicin (17 days, P=0.001) or other controls. In conclusion, the dual-targeting daunorubicin liposomes are able to improve the therapeutic efficacy of brain glioma in vitro and in animals.Copyright 2009 Elsevier B.V. All rights reserved.