Enhanced efficacy of functionalized epirubicin liposomes in treating brain glioma-bearing rats.
OBJECTIVE
The restriction of drug transporting across the blood-brain barrier (BBB) and the limit of drug penetrating into the tumor tissue remain the major obstacles for brain tumor chemotherapy. In the present study, we developed a functionalized liposomal nanoconstruct, epirubicin liposomes modified with tamoxifen (TAM) and transferrin (TF), for transporting drug across the BBB and afterwards targeting the brain glioma.


METHODS
Evaluations were performed on the murine C6 glioma cells, the C6 glioma spheroids, the BBB model in vitro and the brain glioma-bearing rats.


RESULTS
When compared with controls, epirubicin liposomes modified with TAM and TF showed the strongest inhibitory effect to C6 glioma cells or glioma spheroids in vitro, significant transport ability across the BBB model in vitro, an evident effect of targeting the brain tumor cells in vitro, and an extended median survival time in the brain glioma-bearing rats.


CONCLUSIONS
Epirubicin liposomes modified with TAM and TF significantly improve the therapeutic efficacy of brain glioma in vitro and in animals, hence providing a new strategy for brain tumor chemotherapy.
Tian
Wei
W
State Key Laboratory of Natural and Biomimetic Drugs, and School of Pharmaceutical Sciences, Peking University, Beijing, China.
Ying
Xue
X
Du
Ju
J
Guo
Jia
J
Men
Ying
Y
Zhang
Yan
Y
Li
Ruo-Jing
RJ
Yao
Hong-Juan
HJ
Lou
Jin-Ning
JN
Zhang
Liang-Ren
LR
Lu
Wan-Liang
WL
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001812:Blood-Brain Barrier; D001932:Brain Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D015251:Epirubicin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005910:Glioma / Q000188:drug therapy*; D008081:Liposomes; D051379:Mice; D051381:Rats; D017208:Rats, Wistar
D000970:Antineoplastic Agents; D008081:Liposomes; D015251:Epirubicin