Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 463, Issue 1, Pages 81-88Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2013.12.046
Keywords
Cholangiocarcinoma; Micelle; Amphiphilic block copolymer; Thermo sensitive; Drug carriers
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Funding
- Shanghai Science and Technology Commission [08JC1416200]
- Nano Science and Technology Special Funding of Shanghai Science and Technology Commission [0952nm03600]
- National Natural Science Foundation of China [81170457]
- National High Technology Research and Development Program of China 863 [2012AA022606]
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Cholangiocarcinoma is an epithelial cancer of the bile ducts with poor prognosis and, in recent years, a rapidly increasing incidence. In this study, nano-sized thermo-sensitive micelles were investigated as drug carriers to improve chemotherapy in cholangiocarcinoma. Thermo-sensitive amphiphilic block copolymer, P-(N,N-isopropylacrylamide-co-N-hydroxymethylacrylamide)-b-caprolactone [P-(NIPAAmco-NHMAAm)-b-PCL] with lower critical solution temperature (LCST) at about 38 C was synthesized. Doxorubicin (DOX)-loaded micelles were prepared by dialysis method. The micelles exhibited a sustained and temperature-dependent DOX release. Toxicity of the blank micelles for human cholangiocarcinoma (QBC939) cells was minimal both in vitro and in vivo. In contrast, the DOX-loaded micelles effectively inhibited proliferation and induced apoptosis of QBC939 cells in vitro (p< 0.05) and inhibited tumor growth in nude mice by 21.49%. These results indicated that thermo-sensitive amphiphilic micelles are a promising and effective drug carrier, and show potential for improving chemotherapy for cholangiocarcinoma. (C) 2014 Elsevier B.V. All rights reserved.
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