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Int J Pharm. 2014 Mar 10;463(1):81-8. doi: 10.1016/j.ijpharm.2013.12.046. Epub 2014 Jan 6.

Investigation of thermo-sensitive amphiphilic micelles as drug carriers for chemotherapy in cholangiocarcinoma in vitro and in vivo.

Author information

  • 1Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, 1665 Kongjiang Road, Shanghai 200092, PR China.
  • 2Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, 1665 Kongjiang Road, Shanghai 200092, PR China. Electronic address: zhiwquan@yahoo.cn.
  • 3Institute of Nano and Bio-polymeric Materials, School of Material Science and Engineering, Tongji University, Cao An Road 4800, Shanghai 201804, PR China; Key Laboratory Advanced Civil Engineering Materials, Ministry of Education, School of Material Science and Engineering, Tongji University, Cao An Road 4800, Shanghai 201804, PR China. Electronic address: qgtan@tongji.edu.cn.

Abstract

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-(NIPAAm-co-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.

Copyright © 2014 Elsevier B.V. All rights reserved.

KEYWORDS:

Amphiphilic block copolymer; Cholangiocarcinoma; Drug carriers; Micelle; Thermo-sensitive

PMID:
24406676
[PubMed - indexed for MEDLINE]
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