Preparation, characterization and application of star-shaped PCL/PEG micelles for the delivery of doxorubicin in the treatment of colon cancer
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 Wei11Department of Pathophysiology, College of Preclinical and Forensic Medical Sciences, and State Key Laboratory of Biotherapy an...
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Dove Medical Press
2013
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oai:doaj.org-article:8f9a49770d7147378c7332600a50935a2021-12-02T04:46:19ZPreparation, characterization and application of star-shaped PCL/PEG micelles for the delivery of doxorubicin in the treatment of colon cancer1176-91141178-2013https://doaj.org/article/8f9a49770d7147378c7332600a50935a2013-03-01T00:00:00Zhttp://www.dovepress.com/preparation-characterization-and-application-of-star-shaped-pclpeg-mic-a12416https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Xiang 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 Wei11Department 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 ChinaAbstract: 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, CMCGao XWang BLWei XWRao WAi FZhao FMen KYang BWLiu XYHuang MJGou MLQian ZYHuang NWei YQDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss default, Pp 971-982 (2013) |
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DOAJ |
| collection |
DOAJ |
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Medicine (General) R5-920 |
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Medicine (General) R5-920 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 Preparation, characterization and application of star-shaped PCL/PEG micelles for the delivery of doxorubicin in the treatment of colon cancer |
| description |
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 Wei11Department 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 ChinaAbstract: 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 |
| format |
article |
| author |
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 |
| author_facet |
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 |
| author_sort |
Gao X |
| title |
Preparation, characterization and application of star-shaped PCL/PEG micelles for the delivery of doxorubicin in the treatment of colon cancer |
| title_short |
Preparation, characterization and application of star-shaped PCL/PEG micelles for the delivery of doxorubicin in the treatment of colon cancer |
| title_full |
Preparation, characterization and application of star-shaped PCL/PEG micelles for the delivery of doxorubicin in the treatment of colon cancer |
| title_fullStr |
Preparation, characterization and application of star-shaped PCL/PEG micelles for the delivery of doxorubicin in the treatment of colon cancer |
| title_full_unstemmed |
Preparation, characterization and application of star-shaped PCL/PEG micelles for the delivery of doxorubicin in the treatment of colon cancer |
| title_sort |
preparation, characterization and application of star-shaped pcl/peg micelles for the delivery of doxorubicin in the treatment of colon cancer |
| publisher |
Dove Medical Press |
| publishDate |
2013 |
| url |
https://doaj.org/article/8f9a49770d7147378c7332600a50935a |
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