PUBLICATION

Improving anticancer activity and reducing systemic toxicity of doxorubicin by self-assembled polymeric micelles

Authors
Gou, M., Shi, H., Guo, G., Men, K., Zhang, J., Zheng, L., Li, Z., Luo, F., Qian, Z., Zhao, X., and Wei, Y.
ID
ZDB-PUB-110131-32
Date
2011
Source
Nanotechnology   22(9): 095102 (Journal)
Registered Authors
Zhao, Xia
Keywords
none
MeSH Terms
  • Animals
  • Antibiotics, Antineoplastic/adverse effects
  • Antibiotics, Antineoplastic/chemistry
  • Antibiotics, Antineoplastic/therapeutic use
  • Cell Line, Tumor
  • Colonic Neoplasms/drug therapy*
  • Colonic Neoplasms/pathology*
  • Doxorubicin/adverse effects
  • Doxorubicin/chemistry*
  • Doxorubicin/therapeutic use*
  • Drug Carriers/chemistry*
  • Female
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Micelles
  • Polyesters/chemistry*
  • Polyethylene Glycols/chemistry*
  • Treatment Outcome
PubMed
21270494 Full text @ Nanotechnology
Abstract
In an attempt to improve anticancer activity and reduce systemic toxicity of doxorubicin (Dox), we encapsulated Dox in monomethoxy poly(ethylene glycol)-poly(ยต-caprolactone) (MPEG-PCL) micelles by a novel self-assembly procedure without using surfactants, organic solvents or vigorous stirring. These Dox encapsulated MPEG-PCL (Dox/MPEG-PCL) micelles with drug loading of 4.2% were monodisperse and < 20 nm in diameter. The Dox can be released from the Dox/MPEG-PCL micelles; the Dox-release at pH 5.5 was faster than that at pH 7.0. Encapsulation of Dox in MPEG-PCL micelles enhanced the cellular uptake and cytotoxicity of Dox on the C-26 colon carcinoma cell in vitro, and slowed the extravasation of Dox in the transgenic zebrafish model. Compared to free Dox, Dox/MPEG-PCL micelles were more effective in inhibiting tumor growth in the subcutaneous C-26 colon carcinoma and Lewis lung carcinoma models, and prolonging survival of mice bearing these tumors. Dox/MPEG-PCL micelles also induced lower systemic toxicity than free Dox. In conclusion, incorporation of Dox in MPEG-PCL micelles enhanced the anticancer activity and decreased the systemic toxicity of Dox; these Dox/MPEG-PCL micelles are an interesting formulation of Dox and may have potential clinical applications in cancer therapy.
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Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping