Pluronic mixed micelles overcoming methotrexate multidrug resistance: in vitro and in vivo evaluation

Yanzuo Chen,1 Xianyi Sha,1 Wei Zhang,1,2 Weitong Zhong,1 Zhuoyang Fan,1 Qiuyue Ren,1 Liangcen Chen,1 Xiaoling Fang1 1Key Laboratory of Smart Drug Delivery, Ministry of Education and PLA, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, People’s Republic of China...

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Autores principales:	Chen Y, Sha X, Zhang W, Zhong W, Fan Z, Ren Q, Chen L, Fang X
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/e695ad7823c24421ad3479b01b0e7d05
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spelling	oai:doaj.org-article:e695ad7823c24421ad3479b01b0e7d052021-12-02T07:12:00ZPluronic mixed micelles overcoming methotrexate multidrug resistance: in vitro and in vivo evaluation1176-91141178-2013https://doaj.org/article/e695ad7823c24421ad3479b01b0e7d052013-04-01T00:00:00Zhttp://www.dovepress.com/pluronic-mixed-micelles-overcoming-methotrexate-multidrug-resistance-i-a12778https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Yanzuo Chen,1 Xianyi Sha,1 Wei Zhang,1,2 Weitong Zhong,1 Zhuoyang Fan,1 Qiuyue Ren,1 Liangcen Chen,1 Xiaoling Fang1 1Key Laboratory of Smart Drug Delivery, Ministry of Education and PLA, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, People’s Republic of China 2Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA Abstract: A Pluronic polymeric mixed micelle delivery system was developed in this study by using Pluronic P105 and F127 block copolymers to encapsulate the antitumor compound, methotrexate (MTX). The MTX-loaded Pluronic P105/F127 mixed micelle exhibited the spherical shape with about 22 nm in diameter, high encapsulation efficiency (about 85%) and pH-dependent in vitro drug release. In this study, A-549 and KBv cell lines were selected as multidrug resistance tumor cell models, while H-460 and KB cell lines were chosen as sensitive tumor cells. The MTX-loaded Pluronic P105/F127 mixed micelle exhibited significant higher in vitro cytotoxicity in multidrug resistant tumor cells than that of control (MTX injection) mainly because of higher cellular uptake of MTX. The pharmacokinetic studies indicated that the Pluronic micelles significantly prolonged systemic circulation time of MTX compared to MTX injection. Moreover, a much stronger antitumor efficacy in KBv tumor xenografts nude mice was observed in the MTX-loaded Pluronic P105/F127 mixed micelle group, than MTX. Collectively, Pluronic P105/F127 mixed micelles could significantly enhance the antitumor activity of MTX and might be a promising drug delivery platform for multidrug resistance modulation. Keywords: multidrug resistance, drug delivery system, micelles, Pluronic, methotrexateChen YSha XZhang WZhong WFan ZRen QChen LFang XDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss default, Pp 1463-1476 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Chen Y Sha X Zhang W Zhong W Fan Z Ren Q Chen L Fang X Pluronic mixed micelles overcoming methotrexate multidrug resistance: in vitro and in vivo evaluation
description	Yanzuo Chen,1 Xianyi Sha,1 Wei Zhang,1,2 Weitong Zhong,1 Zhuoyang Fan,1 Qiuyue Ren,1 Liangcen Chen,1 Xiaoling Fang1 1Key Laboratory of Smart Drug Delivery, Ministry of Education and PLA, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, People’s Republic of China 2Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA Abstract: A Pluronic polymeric mixed micelle delivery system was developed in this study by using Pluronic P105 and F127 block copolymers to encapsulate the antitumor compound, methotrexate (MTX). The MTX-loaded Pluronic P105/F127 mixed micelle exhibited the spherical shape with about 22 nm in diameter, high encapsulation efficiency (about 85%) and pH-dependent in vitro drug release. In this study, A-549 and KBv cell lines were selected as multidrug resistance tumor cell models, while H-460 and KB cell lines were chosen as sensitive tumor cells. The MTX-loaded Pluronic P105/F127 mixed micelle exhibited significant higher in vitro cytotoxicity in multidrug resistant tumor cells than that of control (MTX injection) mainly because of higher cellular uptake of MTX. The pharmacokinetic studies indicated that the Pluronic micelles significantly prolonged systemic circulation time of MTX compared to MTX injection. Moreover, a much stronger antitumor efficacy in KBv tumor xenografts nude mice was observed in the MTX-loaded Pluronic P105/F127 mixed micelle group, than MTX. Collectively, Pluronic P105/F127 mixed micelles could significantly enhance the antitumor activity of MTX and might be a promising drug delivery platform for multidrug resistance modulation. Keywords: multidrug resistance, drug delivery system, micelles, Pluronic, methotrexate
format	article
author	Chen Y Sha X Zhang W Zhong W Fan Z Ren Q Chen L Fang X
author_facet	Chen Y Sha X Zhang W Zhong W Fan Z Ren Q Chen L Fang X
author_sort	Chen Y
title	Pluronic mixed micelles overcoming methotrexate multidrug resistance: in vitro and in vivo evaluation
title_short	Pluronic mixed micelles overcoming methotrexate multidrug resistance: in vitro and in vivo evaluation
title_full	Pluronic mixed micelles overcoming methotrexate multidrug resistance: in vitro and in vivo evaluation
title_fullStr	Pluronic mixed micelles overcoming methotrexate multidrug resistance: in vitro and in vivo evaluation
title_full_unstemmed	Pluronic mixed micelles overcoming methotrexate multidrug resistance: in vitro and in vivo evaluation
title_sort	pluronic mixed micelles overcoming methotrexate multidrug resistance: in vitro and in vivo evaluation
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/e695ad7823c24421ad3479b01b0e7d05
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_version_	1718399608444420096

Pluronic mixed micelles overcoming methotrexate multidrug resistance: in vitro and in vivo evaluation

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