Cancers 2011, 3(1), 61-78; doi:10.3390/cancers3010061
Article

Doxorubicin-Loaded PEG-PCL-PEG Micelle Using Xenograft Model of Nude Mice: Effect of Multiple Administration of Micelle on the Suppression of Human Breast Cancer

Nguyen-Van Cuong 1,2 email, Jian-Lin Jiang 1 email, Yu-Lun Li 1 email, Jim-Ray Chen 3 email, Shyh-Chuan Jwo 4 email and Ming-Fa Hsieh 1,* email
1 Department of Biomedical Engineering, Chung Yuan Christian University, 200, Chung Pei Rd., Chung Li, Taiwan 2 Department of Chemical Engineering, Ho Chi Minh City University of Industry, 12 Nguyen Van Bao St, Ho Chi Minh, Vietnam 3 Department of Pathology, Chang Gung Memorial Hospital at Keelung, Taiwan and Chang Gung University, College of Medicine, Taoyuan, Taiwan 4 Division of General Surgery, Chang Gung Memorial Hospital at Keelung, Taiwan and Chang Gung University, College of Medicine, Taoyuan, Taiwan
* Author to whom correspondence should be addressed.
Received: 11 November 2010; in revised form: 20 December 2010 / Accepted: 27 December 2010 / Published: 28 December 2010
(This article belongs to the Special Issue Nanotechnology and Cancer Therapeutics)
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Abstract: The triblock copolymer is composed of two identical hydrophilic segments: Monomethoxy poly(ethylene glycol) (mPEG) and one hydrophobic segment poly(ε‑caprolactone) (PCL); which is synthesized by coupling of mPEG-PCL-OH and mPEG‑COOH in a mild condition using dicyclohexylcarbodiimide and 4-dimethylamino pyridine. The amphiphilic block copolymer can self-assemble into nanoscopic micelles to accommodate doxorubixin (DOX) in the hydrophobic core. The physicochemical properties and in vitro tests, including cytotoxicity of the micelles, have been characterized in our previous study. In this study, DOX was encapsulated into micelles with a drug loading content of 8.5%. Confocal microscopy indicated that DOX was internalized into the cytoplasm via endocystosis. A dose-finding scheme of the polymeric micelle (placebo) showed a safe dose of PEG-PCL-PEG micelles was 71.4 mg/kg in mice. Importantly, the circulation time of DOX-loaded micelles in the plasma significantly increased compared to that of free DOX in rats. A biodistribution study displayed that plasma extravasation of DOX in liver and spleen occurred in the first four hours. Lastly, the tumor growth of human breast cancer cells in nude mice was suppressed by multiple injections (5 mg/kg, three times daily on day 0, 7 and 14) of DOX-loaded micelles as compared to multiple administrations of free DOX.
Keywords: nanoparticles; drug delivery system; monomethoxy poly(ethylene glycol); poly(ε-caprolactone); safety evaluation; biodistribution; antitumor activity

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Cite This Article

MDPI and ACS Style

Cuong, N.-V.; Jiang, J.-L.; Li, Y.-L.; Chen, J.-R.; Jwo, S.-C.; Hsieh, M.-F. Doxorubicin-Loaded PEG-PCL-PEG Micelle Using Xenograft Model of Nude Mice: Effect of Multiple Administration of Micelle on the Suppression of Human Breast Cancer. Cancers 2011, 3, 61-78.

AMA Style

Cuong N-V, Jiang J-L, Li Y-L, Chen J-R, Jwo S-C, Hsieh M-F. Doxorubicin-Loaded PEG-PCL-PEG Micelle Using Xenograft Model of Nude Mice: Effect of Multiple Administration of Micelle on the Suppression of Human Breast Cancer. Cancers. 2011; 3(1):61-78.

Chicago/Turabian Style

Cuong, Nguyen-Van; Jiang, Jian-Lin; Li, Yu-Lun; Chen, Jim-Ray; Jwo, Shyh-Chuan; Hsieh, Ming-Fa. 2011. "Doxorubicin-Loaded PEG-PCL-PEG Micelle Using Xenograft Model of Nude Mice: Effect of Multiple Administration of Micelle on the Suppression of Human Breast Cancer." Cancers 3, no. 1: 61-78.

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