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Preparation, characterization and application of star-shaped PCL/PEG micelles for the delivery of doxorubicin in the treatment of colon cancer

Authors Gao X, Wang BL, Wei XW, Rao W, Ai F, Zhao F, Men K, Yang BW, Liu XY, Huang MJ, Gou ML, Qian ZY, Huang N, Wei YQ

Received 24 October 2012

Accepted for publication 24 November 2012

Published 8 March 2013 Volume 2013:8(1) Pages 971—982

DOI https://doi.org/10.2147/IJN.S39532

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Xiang Gao,1 BiLan Wang,1 XiaWei Wei,1 Wang Rao,2 Fang Ai,2 Fen Zhao,2 Ke Men,1 Bowen Yang,1 Xingyu Liu,1 Meijuan Huang,1 Maling Gou,1 ZhiYong Qian,1 Ning Huang,1 Yuquan Wei1

1Department of Pathophysiology, College of Preclinical and Forensic Medical Sciences, and State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China; 2Department of Surgery, First Affiliated Hospital, Xinxiang Medical School, Xinxiang, People's Republic of China

Abstract: Star-shaped polymer micelles have good stability against dilution with water, showing promising application in drug delivery. In this work, biodegradable micelles made from star-shaped poly
(ε-caprolactone)/poly(ethylene glycol) (PCL/PEG) copolymer were prepared and used to deliver doxorubicin (Dox) in vitro and in vivo. First, an acrylated monomethoxy poly (ethylene glycol)-poly
(ε-caprolactone) (MPEG-PCL) diblock copolymer was synthesized, which then self-assembled into micelles, with a core-shell structure, in water. Then, the double bonds at the end of the PCL blocks were conjugated together by radical polymerization, forming star-shaped MPEG-PCL (SSMPEG-PCL) micelles. These SSMPEG-PCL micelles were monodispersed (polydispersity index = 0.11), with mean diameter of 25 nm, in water. Blank SSMPEG-PCL micelles had little cytotoxicity and did not induce obvious hemolysis in vitro. The critical micelle concentration of the SSMPEG-PCL micelles was five times lower than that of the MPEG-PCL micelles. Dox was directly loaded into SSMPEG-PCL micelles by a pH-induced self-assembly method. Dox loading did not significantly affect the particle size of SSMPEG-PCL micelles. Dox-loaded SSMPEG-PCL (Dox/SSMPEG-PCL) micelles slowly released Dox in vitro, and the Dox release at pH 5.5 was faster than that at pH 7.0. Also, encapsulation of Dox in SSMPEG-PCL micelles enhanced the anticancer activity of Dox in vitro. Furthermore, the therapeutic efficiency of Dox/SSMPEG-PCL on colon cancer mouse model was evaluated. Dox/SSMPEG-PCL caused a more significant inhibitory effect on tumor growth than did free Dox or controls (P < 0.05), which indicated that Dox/SSMPEG-PCL had enhanced anticolon cancer activity in vivo. Analysis with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) showed that Dox/SSMPEG-PCL induced more tumor cell apoptosis than free Dox or controls. These results suggested that SSMPEG-PCL micelles have promising application in doxorubicin delivery for the enhancement of anticancer effect.
Keywords: drug delivery, star-shaped polymer, MPEG-PCL, CMC

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