Effects of X-shaped reduction-sensitive amphiphilic block copolymer on drug delivery

Haijun Xiao, Lu WangState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, People’s Republic of ChinaAbstract: To study the effects of X-shaped amphiphilic block copolymers on delivery of docetaxel (DTX) and the redu...

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Autores principales:	Xiao H, Wang L
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/d6ac6b966e78481cbaff84304a3dc69e
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spelling	oai:doaj.org-article:d6ac6b966e78481cbaff84304a3dc69e2021-12-02T05:10:44ZEffects of X-shaped reduction-sensitive amphiphilic block copolymer on drug delivery1178-2013https://doaj.org/article/d6ac6b966e78481cbaff84304a3dc69e2015-08-01T00:00:00Zhttp://www.dovepress.com/effects-of-x-shaped-reduction-sensitive-amphiphilic-block-copolymer-on-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Haijun Xiao, Lu WangState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, People’s Republic of ChinaAbstract: To study the effects of X-shaped amphiphilic block copolymers on delivery of docetaxel (DTX) and the reduction-sensitive property on drug release, a novel reduction-sensitive amphiphilic copolymer, (PLGA)2-SS-4-arm-PEG2000 with a Gemini-like X-shape, was successfully synthesized. The formation of nanomicelles was proved with respect to the blue shift of the emission fluorescence as well as the fluorescent intensity increase of coumarin 6-loaded particles. The X-shaped polymers exhibited a smaller critical micelle concentration value and possessed higher micellar stability in comparison with those of linear ones. The size of X-shaped (PLGA)2-SS-4-arm-PEG2000 polymer nanomicelles (XNMs) was much smaller than that of nanomicelles prepared with linear polymers. The reduction sensitivity of polymers was confirmed by the increase of micellar sizes as well as the in vitro drug release profile of DTX-loaded XNMs (DTX/XNMs). Cytotoxicity assays in vitro revealed that the blank XNMs were nontoxic against A2780 cells up to a concentration of 50 µg/mL, displaying good biocompatibility. DTX/XNMs were more toxic against A2780 cells than other formulations in both dose- and time-dependent manners. Cellular uptake assay displayed a higher intracellular drug delivery efficiency of XNMs than that of nanomicelles prepared with linear polymers. Besides, the promotion of tubulin polymerization induced by DTX was visualized by immunofluorescence analysis, and the acceleration of apoptotic process against A2780 cells was also imaged using a fluorescent staining method. Therefore, this X-shaped reduction-sensitive (PLGA)2-SS-4-arm-PEG2000 copolymer could effectively improve the micellar stability and significantly enhance the therapeutic efficacy of DTX by increasing the cellular uptake and selectively accelerating the drug release inside cancer cells.Keywords: PLGA, 4-arm PEG, micelle, stability, uptakeXiao HWang LDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 5309-5325 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Xiao H Wang L Effects of X-shaped reduction-sensitive amphiphilic block copolymer on drug delivery
description	Haijun Xiao, Lu WangState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, People’s Republic of ChinaAbstract: To study the effects of X-shaped amphiphilic block copolymers on delivery of docetaxel (DTX) and the reduction-sensitive property on drug release, a novel reduction-sensitive amphiphilic copolymer, (PLGA)2-SS-4-arm-PEG2000 with a Gemini-like X-shape, was successfully synthesized. The formation of nanomicelles was proved with respect to the blue shift of the emission fluorescence as well as the fluorescent intensity increase of coumarin 6-loaded particles. The X-shaped polymers exhibited a smaller critical micelle concentration value and possessed higher micellar stability in comparison with those of linear ones. The size of X-shaped (PLGA)2-SS-4-arm-PEG2000 polymer nanomicelles (XNMs) was much smaller than that of nanomicelles prepared with linear polymers. The reduction sensitivity of polymers was confirmed by the increase of micellar sizes as well as the in vitro drug release profile of DTX-loaded XNMs (DTX/XNMs). Cytotoxicity assays in vitro revealed that the blank XNMs were nontoxic against A2780 cells up to a concentration of 50 µg/mL, displaying good biocompatibility. DTX/XNMs were more toxic against A2780 cells than other formulations in both dose- and time-dependent manners. Cellular uptake assay displayed a higher intracellular drug delivery efficiency of XNMs than that of nanomicelles prepared with linear polymers. Besides, the promotion of tubulin polymerization induced by DTX was visualized by immunofluorescence analysis, and the acceleration of apoptotic process against A2780 cells was also imaged using a fluorescent staining method. Therefore, this X-shaped reduction-sensitive (PLGA)2-SS-4-arm-PEG2000 copolymer could effectively improve the micellar stability and significantly enhance the therapeutic efficacy of DTX by increasing the cellular uptake and selectively accelerating the drug release inside cancer cells.Keywords: PLGA, 4-arm PEG, micelle, stability, uptake
format	article
author	Xiao H Wang L
author_facet	Xiao H Wang L
author_sort	Xiao H
title	Effects of X-shaped reduction-sensitive amphiphilic block copolymer on drug delivery
title_short	Effects of X-shaped reduction-sensitive amphiphilic block copolymer on drug delivery
title_full	Effects of X-shaped reduction-sensitive amphiphilic block copolymer on drug delivery
title_fullStr	Effects of X-shaped reduction-sensitive amphiphilic block copolymer on drug delivery
title_full_unstemmed	Effects of X-shaped reduction-sensitive amphiphilic block copolymer on drug delivery
title_sort	effects of x-shaped reduction-sensitive amphiphilic block copolymer on drug delivery
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/d6ac6b966e78481cbaff84304a3dc69e
work_keys_str_mv	AT xiaoh effectsofxshapedreductionsensitiveamphiphilicblockcopolymerondrugdelivery AT wangl effectsofxshapedreductionsensitiveamphiphilicblockcopolymerondrugdelivery
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Effects of X-shaped reduction-sensitive amphiphilic block copolymer on drug delivery

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