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

Abstract

In an attempt to improve anticancer activity and reduce systemic toxicity of doxorubicin (Dox), we encapsulated Dox in monomethoxy poly(ethylene glycol)-poly(ε-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.

• Authors: MaLing Gou, HuaShan Shi, Gang Guo, Ke Men, Juan Zhang, Lan Zheng, ZhiYong Li, Feng Luo, ZhiYong Qian, Xia Zhao, YuQuan Wei
• Journal: Nanotechnology (Nanotechnology) Vol. 22 Issue 9 Pg. 095102 (Mar 04 2011) ISSN: 1361-6528 [Electronic] England
• PMID: 21270494 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibiotics, Antineoplastic
• Drug Carriers
• Micelles
• Polyesters
• poly(ethylene glycol)-poly(caprolactone)-poly(ethylene glycol)
• Polyethylene Glycols
• Doxorubicin

Topics

• Animals
• Antibiotics, Antineoplastic (adverse effects, chemistry, therapeutic use)
• Cell Line, Tumor
• Colonic Neoplasms (drug therapy, pathology)
• Doxorubicin (adverse effects, chemistry, therapeutic use)
• Drug Carriers (chemistry)
• Female
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Micelles
• Polyesters (chemistry)
• Polyethylene Glycols (chemistry)
• Treatment Outcome