Pluronic P105/F127 mixed micelles for the delivery of docetaxel against Taxol-resistant non-small cell lung cancer: optimization and in vitro, in vivo evaluation

Liangcen Chen, Xianyi Sha, Xinyi Jiang, Yanzuo Chen, Qiuyue Ren, Xiaoling FangDepartment of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, ChinaAbstract: The aim of this work was to establish a novel polymeric mixed micelle composed of Pluronic P105 and F127 copolymers loaded with th...

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Autores principales:	Fang X, Ren Q, Chen Y, Jiang X, Sha X, Chen L
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/bdd941b712c74d82be27cd6b9b1b7671
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spelling	oai:doaj.org-article:bdd941b712c74d82be27cd6b9b1b76712021-12-02T05:49:43ZPluronic P105/F127 mixed micelles for the delivery of docetaxel against Taxol-resistant non-small cell lung cancer: optimization and in vitro, in vivo evaluation1176-91141178-2013https://doaj.org/article/bdd941b712c74d82be27cd6b9b1b76712013-01-01T00:00:00Zhttp://www.dovepress.com/pluronic-p105f127-mixed-micelles-for-the-delivery-of-docetaxel-against-a11850https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Liangcen Chen, Xianyi Sha, Xinyi Jiang, Yanzuo Chen, Qiuyue Ren, Xiaoling FangDepartment of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, ChinaAbstract: The aim of this work was to establish a novel polymeric mixed micelle composed of Pluronic P105 and F127 copolymers loaded with the poorly soluble antitumor drug docetaxel (DTX) against Taxol-resistant non-small cell lung cancer. A central composite design was utilized to optimize the preparation process, helping to improve drug solubilization efficiency and micelle stability. Prepared by a thin-film hydration method, the average size of the optimized mixed micelle was 23 nm, with a 92.40% encapsulation ratio and a 1.81% drug-loading efficiency. The optimized formulation showed high storage stability in lyophilized form, with 95.7% of the drug content remaining after 6 months&#39; storage at 4&deg;C. The in vitro cytotoxicity assay showed that the IC50 values for Taxotere&reg; and mixed micelles were similar for A549, while on A549/Taxol cell lines, DTX-loaded P105/F127 mixed micelles showed a superior hypersensitizing effect; their IC50 value (0.059 &micro;g/mL) was greatly reduced compared to those of Taxotere injections (0.593 &micro;g/mL). The in vivo pharmacokinetic study showed that the mixed-micelle formulation achieved a 1.85-fold longer mean residence time in circulation and a 3.82-fold larger area under the plasma concentration-time curve than Taxotere. In addition, therapeutic improvement of mixed micelles in vivo against A549/Taxol was obtained. The tumor inhibition rate of the micelles was 69.05%, versus 34.43% for Taxotere (P &lt; 0.01). Therefore, it could be concluded from the results that DTX-loaded P105/F127 mixed micelles might serve as a potential antitumor drug delivery system to overcome multidrug resistance in lung cancer.Keywords: docetaxel, polymeric micelle, pluronic, multi-drug resistanceFang XRen QChen YJiang XSha XChen LDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss default, Pp 73-84 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Fang X Ren Q Chen Y Jiang X Sha X Chen L Pluronic P105/F127 mixed micelles for the delivery of docetaxel against Taxol-resistant non-small cell lung cancer: optimization and in vitro, in vivo evaluation
description	Liangcen Chen, Xianyi Sha, Xinyi Jiang, Yanzuo Chen, Qiuyue Ren, Xiaoling FangDepartment of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, ChinaAbstract: The aim of this work was to establish a novel polymeric mixed micelle composed of Pluronic P105 and F127 copolymers loaded with the poorly soluble antitumor drug docetaxel (DTX) against Taxol-resistant non-small cell lung cancer. A central composite design was utilized to optimize the preparation process, helping to improve drug solubilization efficiency and micelle stability. Prepared by a thin-film hydration method, the average size of the optimized mixed micelle was 23 nm, with a 92.40% encapsulation ratio and a 1.81% drug-loading efficiency. The optimized formulation showed high storage stability in lyophilized form, with 95.7% of the drug content remaining after 6 months&#39; storage at 4&deg;C. The in vitro cytotoxicity assay showed that the IC50 values for Taxotere&reg; and mixed micelles were similar for A549, while on A549/Taxol cell lines, DTX-loaded P105/F127 mixed micelles showed a superior hypersensitizing effect; their IC50 value (0.059 &micro;g/mL) was greatly reduced compared to those of Taxotere injections (0.593 &micro;g/mL). The in vivo pharmacokinetic study showed that the mixed-micelle formulation achieved a 1.85-fold longer mean residence time in circulation and a 3.82-fold larger area under the plasma concentration-time curve than Taxotere. In addition, therapeutic improvement of mixed micelles in vivo against A549/Taxol was obtained. The tumor inhibition rate of the micelles was 69.05%, versus 34.43% for Taxotere (P &lt; 0.01). Therefore, it could be concluded from the results that DTX-loaded P105/F127 mixed micelles might serve as a potential antitumor drug delivery system to overcome multidrug resistance in lung cancer.Keywords: docetaxel, polymeric micelle, pluronic, multi-drug resistance
format	article
author	Fang X Ren Q Chen Y Jiang X Sha X Chen L
author_facet	Fang X Ren Q Chen Y Jiang X Sha X Chen L
author_sort	Fang X
title	Pluronic P105/F127 mixed micelles for the delivery of docetaxel against Taxol-resistant non-small cell lung cancer: optimization and in vitro, in vivo evaluation
title_short	Pluronic P105/F127 mixed micelles for the delivery of docetaxel against Taxol-resistant non-small cell lung cancer: optimization and in vitro, in vivo evaluation
title_full	Pluronic P105/F127 mixed micelles for the delivery of docetaxel against Taxol-resistant non-small cell lung cancer: optimization and in vitro, in vivo evaluation
title_fullStr	Pluronic P105/F127 mixed micelles for the delivery of docetaxel against Taxol-resistant non-small cell lung cancer: optimization and in vitro, in vivo evaluation
title_full_unstemmed	Pluronic P105/F127 mixed micelles for the delivery of docetaxel against Taxol-resistant non-small cell lung cancer: optimization and in vitro, in vivo evaluation
title_sort	pluronic p105/f127 mixed micelles for the delivery of docetaxel against taxol-resistant non-small cell lung cancer: optimization and in vitro, in vivo evaluation
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/bdd941b712c74d82be27cd6b9b1b7671
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Pluronic P105/F127 mixed micelles for the delivery of docetaxel against Taxol-resistant non-small cell lung cancer: optimization and in vitro, in vivo evaluation

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