Doxorubicin-loaded PEG-PCL copolymer micelles enhance cytotoxicity and intracellular accumulation of doxorubicin in adriamycin-resistant tumor cells

Yuan-Yuan Diao1,2,*, Hao-Ying Li3,*, Ying-Hua Fu4, Min Han1, Yu-Lan Hu1, Hong-Liang Jiang5, Yasuo Tsutsumi6, Qi-Chun Wei7, Da-Wei Chen2, Jian-Qing Gao1 1Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou; 2School of Pharmacy, Shenyang Pharmaceutical Univers...

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Autores principales:	Diao YY, Li HY, Fu YH, Han M, Hu YL, Jiang HL, Tsutsumi Y, Wei QC, Chen DW, Gao JQ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2011
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/c859618f4691467287658f5510df2607
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spelling	oai:doaj.org-article:c859618f4691467287658f5510df26072021-12-02T06:38:06ZDoxorubicin-loaded PEG-PCL copolymer micelles enhance cytotoxicity and intracellular accumulation of doxorubicin in adriamycin-resistant tumor cells1176-91141178-2013https://doaj.org/article/c859618f4691467287658f5510df26072011-09-01T00:00:00Zhttp://www.dovepress.com/doxorubicin-loaded-peg-pcl-copolymer-micelles-enhance-cytotoxicity-and-a8266https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Yuan-Yuan Diao1,2,, Hao-Ying Li3,, Ying-Hua Fu4, Min Han1, Yu-Lan Hu1, Hong-Liang Jiang5, Yasuo Tsutsumi6, Qi-Chun Wei7, Da-Wei Chen2, Jian-Qing Gao1 1Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou; 2School of Pharmacy, Shenyang Pharmaceutical University, Shenyang; 3Biomanufacturing Research Centre, Department of Mechanical and Electrical Engineering, Soochow University, Suzhou; 4Department of Pharmaceutics, Jiaxing University College of Medicine, Jiaxing; 5Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, People&#39;s Republic of China; 6Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan; 7Department of Radiation Oncology, Ministry of Education Key Laboratory of Cancer Prevention and Intervention, Zhejiang University School of Medicine, Hangzhou, People&#39;s Republic of China, *These authors contributed equally to this workBackground: Multidrug resistance remains a major obstacle to successful cancer chemotherapy. Some chemical multidrug resistance inhibitors, such as ciclosporin and verapamil, have been reported to reverse resistance in tumor cells. However, the accompanying side effects have limited their clinical application. In this study, we have developed a novel drug delivery system, ie, a polyethyleneglycol-polycaprolactone (PEG-PCL) copolymer micelle encapsulating doxorubicin, in order to circumvent drug resistance in adriamycin-resistant K562 tumor cells.Methods: Doxorubicin-loaded diblock copolymer PEG-PCL micelles were developed, and the physicochemical properties of these micelles, and accumulation and cytotoxicity of doxorubicin in adriamycin-resistant K562 tumor cells were studied.Results: Doxorubicin-loaded micelles were prepared using a solvent evaporation method with a diameter of 36 nm and a zeta potential of +13.8 mV. The entrapment efficiency of doxorubicin was 48.6% &plusmn; 2.3%. The micelles showed sustained release, increased uptake, and cellular cytotoxicity, as well as decreased efflux of doxorubicin in adriamycin-resistant K562 tumor cells.Conclusion: This study suggests that PEG-PCL micelles have the potential to reverse multidrug resistance in tumor cells.Keywords: doxorubicin, polyethylene glycol, polycaprolactone, adriamycin-resistant K562 tumor cells, multidrug resistance, micellesDiao YYLi HYFu YHHan MHu YLJiang HLTsutsumi YWei QCChen DWGao JQDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2011, Iss default, Pp 1955-1962 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Diao YY Li HY Fu YH Han M Hu YL Jiang HL Tsutsumi Y Wei QC Chen DW Gao JQ Doxorubicin-loaded PEG-PCL copolymer micelles enhance cytotoxicity and intracellular accumulation of doxorubicin in adriamycin-resistant tumor cells
description	Yuan-Yuan Diao1,2,, Hao-Ying Li3,, Ying-Hua Fu4, Min Han1, Yu-Lan Hu1, Hong-Liang Jiang5, Yasuo Tsutsumi6, Qi-Chun Wei7, Da-Wei Chen2, Jian-Qing Gao1 1Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou; 2School of Pharmacy, Shenyang Pharmaceutical University, Shenyang; 3Biomanufacturing Research Centre, Department of Mechanical and Electrical Engineering, Soochow University, Suzhou; 4Department of Pharmaceutics, Jiaxing University College of Medicine, Jiaxing; 5Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, People&#39;s Republic of China; 6Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan; 7Department of Radiation Oncology, Ministry of Education Key Laboratory of Cancer Prevention and Intervention, Zhejiang University School of Medicine, Hangzhou, People&#39;s Republic of China, *These authors contributed equally to this workBackground: Multidrug resistance remains a major obstacle to successful cancer chemotherapy. Some chemical multidrug resistance inhibitors, such as ciclosporin and verapamil, have been reported to reverse resistance in tumor cells. However, the accompanying side effects have limited their clinical application. In this study, we have developed a novel drug delivery system, ie, a polyethyleneglycol-polycaprolactone (PEG-PCL) copolymer micelle encapsulating doxorubicin, in order to circumvent drug resistance in adriamycin-resistant K562 tumor cells.Methods: Doxorubicin-loaded diblock copolymer PEG-PCL micelles were developed, and the physicochemical properties of these micelles, and accumulation and cytotoxicity of doxorubicin in adriamycin-resistant K562 tumor cells were studied.Results: Doxorubicin-loaded micelles were prepared using a solvent evaporation method with a diameter of 36 nm and a zeta potential of +13.8 mV. The entrapment efficiency of doxorubicin was 48.6% &plusmn; 2.3%. The micelles showed sustained release, increased uptake, and cellular cytotoxicity, as well as decreased efflux of doxorubicin in adriamycin-resistant K562 tumor cells.Conclusion: This study suggests that PEG-PCL micelles have the potential to reverse multidrug resistance in tumor cells.Keywords: doxorubicin, polyethylene glycol, polycaprolactone, adriamycin-resistant K562 tumor cells, multidrug resistance, micelles
format	article
author	Diao YY Li HY Fu YH Han M Hu YL Jiang HL Tsutsumi Y Wei QC Chen DW Gao JQ
author_facet	Diao YY Li HY Fu YH Han M Hu YL Jiang HL Tsutsumi Y Wei QC Chen DW Gao JQ
author_sort	Diao YY
title	Doxorubicin-loaded PEG-PCL copolymer micelles enhance cytotoxicity and intracellular accumulation of doxorubicin in adriamycin-resistant tumor cells
title_short	Doxorubicin-loaded PEG-PCL copolymer micelles enhance cytotoxicity and intracellular accumulation of doxorubicin in adriamycin-resistant tumor cells
title_full	Doxorubicin-loaded PEG-PCL copolymer micelles enhance cytotoxicity and intracellular accumulation of doxorubicin in adriamycin-resistant tumor cells
title_fullStr	Doxorubicin-loaded PEG-PCL copolymer micelles enhance cytotoxicity and intracellular accumulation of doxorubicin in adriamycin-resistant tumor cells
title_full_unstemmed	Doxorubicin-loaded PEG-PCL copolymer micelles enhance cytotoxicity and intracellular accumulation of doxorubicin in adriamycin-resistant tumor cells
title_sort	doxorubicin-loaded peg-pcl copolymer micelles enhance cytotoxicity and intracellular accumulation of doxorubicin in adriamycin-resistant tumor cells
publisher	Dove Medical Press
publishDate	2011
url	https://doaj.org/article/c859618f4691467287658f5510df2607
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Doxorubicin-loaded PEG-PCL copolymer micelles enhance cytotoxicity and intracellular accumulation of doxorubicin in adriamycin-resistant tumor cells

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