Sodium cholate-enhanced polymeric micelle system for tumor-targeting delivery of paclitaxel

Xiaomin Zhang,1,2 Yibo Wu,1 Min Zhang,1 Jing Mao,3 Yun Wu,4 Yingxin Zhang,2 Ju Yao,2 Chang Xu,2 Wenli Guo,1 Bo Yu2 1Beijing Key Laboratory of Special Elastomeric Composite Materials, Beijing Institute of Petrochemical Technology, Beijing, 2Push-Kang Biotechnology, Hangzhou, 3Beijing Key Laboratory...

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Autores principales:	Zhang X, Wu Y, Zhang M, Mao J, Zhang Y, Yao J, Xu C, Guo W, Yu B
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	sodium cholate polymeric micelles enhanced tumor-targeting delivery Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/4f89793cecbd48508b8bce38c2ea4f0a
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spelling	oai:doaj.org-article:4f89793cecbd48508b8bce38c2ea4f0a2021-12-02T07:45:58ZSodium cholate-enhanced polymeric micelle system for tumor-targeting delivery of paclitaxel1178-2013https://doaj.org/article/4f89793cecbd48508b8bce38c2ea4f0a2017-12-01T00:00:00Zhttps://www.dovepress.com/sodium-cholate-enhanced-polymeric-micelle-system-for-tumor-targeting-d-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Xiaomin Zhang,1,2 Yibo Wu,1 Min Zhang,1 Jing Mao,3 Yun Wu,4 Yingxin Zhang,2 Ju Yao,2 Chang Xu,2 Wenli Guo,1 Bo Yu2 1Beijing Key Laboratory of Special Elastomeric Composite Materials, Beijing Institute of Petrochemical Technology, Beijing, 2Push-Kang Biotechnology, Hangzhou, 3Beijing Key Laboratory of Functional Materials for Building Structure and Environment Remediation, Beijing University of Civil Engineering and Architecture, Beijing, China; 4Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY, USA Purpose: Polymeric micelles are attractive nanocarriers for tumor-targeted delivery of paclitaxel (PTX). High antitumor efficacy and low toxicity require that PTX mainly accumulated in tumors with little drug exposure to normal tissues. However, many PTX-loaded micelle formulations suffer from low stability, fast drug release, and lack of tumor-targeting capability in the circulation. To overcome these challenges, we developed a micellar formulation that consists of sodium cholate (NaC) and monomethoxy poly (ethylene glycol)-block-poly (D,L-lactide) (mPEG-PDLLA). Methods: PTX-loaded NaC-mPEG-PDLLA micelles (PTX-CMs) and PTX-loaded mPEG-PDLLA micelles (PTX-Ms) were formulated, and their characteristics, particle size, surface morphology, release behavior in vitro, pharmacokinetics and in vivo biodistributions were researched. In vitro and in vivo tumor inhibition effects were systematically investigated. Furthermore, the hemolysis and acute toxicity of PTX-CMs were also evaluated.Results: The size of PTX-CMs was 53.61±0.75 nm and the ζ-potential was –19.73±0.68 mV. PTX was released much slower from PTX-CMs than PTX-Ms in vitro. Compared with PTX-Ms, the cellular uptake of PTX-CMs was significantly reduced in macrophages and significantly increased in human cancer cells, and therefore, PTX-CMs showed strong growth inhibitory effects on human cancer cells. In vivo, the plasma AUC0–t of PTX-CMs was 1.8-fold higher than that of PTX-Ms, and 5.2-fold higher than that of Taxol. The biodistribution study indicated that more PTX-CMs were accumulated in tumor than PTX-Ms and Taxol. Furthermore, the significant antitumor efficacy of PTX-CMs was observed in mice bearing BEL-7402 hepatocellular carcinoma and A549 lung carcinoma. Results from drug safety assessment studies including acute toxicity and hemolysis test revealed that the PTX-CMs were safe for in vivo applications.Conclusion: These results strongly revealed that NaC-mPEG-PDLLA micelles can tumor-target delivery of PTX and enhance drug penetration in tumor, suggesting that NaC-mPEG-PDLLA micelles are promising nanocarrier systems for anticancer drugs delivery. Keywords: sodium cholate, polymeric micelles, enhanced, tumor-targeting deliveryZhang XWu YZhang MMao JWu YZhang YYao JXu CGuo WYu BDove Medical Pressarticlesodium cholatepolymeric micellesenhancedtumor-targeting deliveryMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 8779-8799 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	sodium cholate polymeric micelles enhanced tumor-targeting delivery Medicine (General) R5-920
spellingShingle	sodium cholate polymeric micelles enhanced tumor-targeting delivery Medicine (General) R5-920 Zhang X Wu Y Zhang M Mao J Wu Y Zhang Y Yao J Xu C Guo W Yu B Sodium cholate-enhanced polymeric micelle system for tumor-targeting delivery of paclitaxel
description	Xiaomin Zhang,1,2 Yibo Wu,1 Min Zhang,1 Jing Mao,3 Yun Wu,4 Yingxin Zhang,2 Ju Yao,2 Chang Xu,2 Wenli Guo,1 Bo Yu2 1Beijing Key Laboratory of Special Elastomeric Composite Materials, Beijing Institute of Petrochemical Technology, Beijing, 2Push-Kang Biotechnology, Hangzhou, 3Beijing Key Laboratory of Functional Materials for Building Structure and Environment Remediation, Beijing University of Civil Engineering and Architecture, Beijing, China; 4Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY, USA Purpose: Polymeric micelles are attractive nanocarriers for tumor-targeted delivery of paclitaxel (PTX). High antitumor efficacy and low toxicity require that PTX mainly accumulated in tumors with little drug exposure to normal tissues. However, many PTX-loaded micelle formulations suffer from low stability, fast drug release, and lack of tumor-targeting capability in the circulation. To overcome these challenges, we developed a micellar formulation that consists of sodium cholate (NaC) and monomethoxy poly (ethylene glycol)-block-poly (D,L-lactide) (mPEG-PDLLA). Methods: PTX-loaded NaC-mPEG-PDLLA micelles (PTX-CMs) and PTX-loaded mPEG-PDLLA micelles (PTX-Ms) were formulated, and their characteristics, particle size, surface morphology, release behavior in vitro, pharmacokinetics and in vivo biodistributions were researched. In vitro and in vivo tumor inhibition effects were systematically investigated. Furthermore, the hemolysis and acute toxicity of PTX-CMs were also evaluated.Results: The size of PTX-CMs was 53.61±0.75 nm and the ζ-potential was –19.73±0.68 mV. PTX was released much slower from PTX-CMs than PTX-Ms in vitro. Compared with PTX-Ms, the cellular uptake of PTX-CMs was significantly reduced in macrophages and significantly increased in human cancer cells, and therefore, PTX-CMs showed strong growth inhibitory effects on human cancer cells. In vivo, the plasma AUC0–t of PTX-CMs was 1.8-fold higher than that of PTX-Ms, and 5.2-fold higher than that of Taxol. The biodistribution study indicated that more PTX-CMs were accumulated in tumor than PTX-Ms and Taxol. Furthermore, the significant antitumor efficacy of PTX-CMs was observed in mice bearing BEL-7402 hepatocellular carcinoma and A549 lung carcinoma. Results from drug safety assessment studies including acute toxicity and hemolysis test revealed that the PTX-CMs were safe for in vivo applications.Conclusion: These results strongly revealed that NaC-mPEG-PDLLA micelles can tumor-target delivery of PTX and enhance drug penetration in tumor, suggesting that NaC-mPEG-PDLLA micelles are promising nanocarrier systems for anticancer drugs delivery. Keywords: sodium cholate, polymeric micelles, enhanced, tumor-targeting delivery
format	article
author	Zhang X Wu Y Zhang M Mao J Wu Y Zhang Y Yao J Xu C Guo W Yu B
author_facet	Zhang X Wu Y Zhang M Mao J Wu Y Zhang Y Yao J Xu C Guo W Yu B
author_sort	Zhang X
title	Sodium cholate-enhanced polymeric micelle system for tumor-targeting delivery of paclitaxel
title_short	Sodium cholate-enhanced polymeric micelle system for tumor-targeting delivery of paclitaxel
title_full	Sodium cholate-enhanced polymeric micelle system for tumor-targeting delivery of paclitaxel
title_fullStr	Sodium cholate-enhanced polymeric micelle system for tumor-targeting delivery of paclitaxel
title_full_unstemmed	Sodium cholate-enhanced polymeric micelle system for tumor-targeting delivery of paclitaxel
title_sort	sodium cholate-enhanced polymeric micelle system for tumor-targeting delivery of paclitaxel
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/4f89793cecbd48508b8bce38c2ea4f0a
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_version_	1718399152719659008

Sodium cholate-enhanced polymeric micelle system for tumor-targeting delivery of paclitaxel

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