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...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2013-04-01
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| Series: | International Journal of Nanomedicine |
| Online Access: | http://www.dovepress.com/pluronic-mixed-micelles-overcoming-methotrexate-multidrug-resistance-i-a12778 |
| _version_ | 1818751004280094720 |
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| 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 |
| collection | DOAJ |
| 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 |
| first_indexed | 2024-12-18T04:28:40Z |
| format | Article |
| id | doaj.art-e695ad7823c24421ad3479b01b0e7d05 |
| institution | Directory Open Access Journal |
| issn | 1176-9114 1178-2013 |
| language | English |
| last_indexed | 2024-12-18T04:28:40Z |
| publishDate | 2013-04-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | International Journal of Nanomedicine |
| spelling | doaj.art-e695ad7823c24421ad3479b01b0e7d052022-12-21T21:21:01ZengDove Medical PressInternational Journal of Nanomedicine1176-91141178-20132013-04-012013default14631476Pluronic mixed micelles overcoming methotrexate multidrug resistance: in vitro and in vivo evaluationChen YSha XZhang WZhong WFan ZRen QChen LFang XYanzuo 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, methotrexatehttp://www.dovepress.com/pluronic-mixed-micelles-overcoming-methotrexate-multidrug-resistance-i-a12778 |
| spellingShingle | 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 International Journal of Nanomedicine |
| title | 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_short | 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 |
| url | http://www.dovepress.com/pluronic-mixed-micelles-overcoming-methotrexate-multidrug-resistance-i-a12778 |
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