Journal
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 41, Issue 2, Pages 232-243Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejps.2010.06.008
Keywords
Functionalized epirubicin liposomes; Tamoxifen; Transferrin; BBB model; Brain glioma-bearing rats
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Funding
- National Basic Research Program of China (973 program) [2007CB935801]
- National Science Foundation of China [20772664]
- National Science Foundation of Beijing [7091006]
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Purpose: 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. Conclusion: 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. (C) 2010 Elsevier B.V. All rights reserved.
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