In vitro and in vivo evaluation of folate receptor-targeting amphiphilic copolymer-modified liposomes loaded with docetaxel

Xiang Li1, Xin Tian2, Jing Zhang3, Xu Zhao1, Xiaohui Chen1, Youhong Jiang2, Dongkai Wang1, Weisan Pan11Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang; 2The Second Laboratory of Cancer Research Institution, The First Hospital of China Medical University,...

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Autores principales:	Li X, Tian X, Zhang J, Zhao X, Chen X, Jiang Y, Wang D, Pan W
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2011
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/959df920be3a4433ae892ff26b390fd4
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spelling	oai:doaj.org-article:959df920be3a4433ae892ff26b390fd42021-12-02T04:52:24ZIn vitro and in vivo evaluation of folate receptor-targeting amphiphilic copolymer-modified liposomes loaded with docetaxel1176-91141178-2013https://doaj.org/article/959df920be3a4433ae892ff26b390fd42011-06-01T00:00:00Zhttp://www.dovepress.com/in-vitro-and-in-vivo-evaluation-of-folate-receptor-targeting-amphiphil-a7629https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Xiang Li1, Xin Tian2, Jing Zhang3, Xu Zhao1, Xiaohui Chen1, Youhong Jiang2, Dongkai Wang1, Weisan Pan11Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang; 2The Second Laboratory of Cancer Research Institution, The First Hospital of China Medical University, Shenyang; 3Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, ChinaBackground: The purpose of this study was to develop folate-poly (PEG-cyanoacrylate-co-cholesteryl cyanoacrylate) (FA-PEG-PCHL)-modified freeze-dried liposomes for targeted chemotherapy using docetaxel as a model drug.Methods: FA-PEG-PCHL was synthesized and its cytotoxicity was evaluated by CCK-8 assay in L929. Docetaxel-loaded liposomes modified by FA-PEG-PCHL were prepared by an organic solvent injection method and lyophilized to obtain freeze-dried FA-PEG-PCHL-docetaxel liposomes (FA-PDCT-L). Two carcinoma cell lines (MCF-7 and A-549 cells) were cultured with docetaxel solution, conventional docetaxel-loaded liposomes, or FA-PDCT-L, and the cytotoxicity and apoptosis was evaluated for each preparation. The uptake of the docetaxel preparations into MCF-7 cells was studied by confocal laser scanning microscopy. Liquid chromatography-mass spectrometry was used to study the pharmacokinetics and tissue distribution characteristics of the preparations.Results: The existence of an enlarged fixed aqueous layer on the surface of the liposomes was affirmed by zeta potential analysis. The entrapment efficiency and particle size distribution were almost the same as those of docetaxel-loaded liposomes. The drug release profile showed that the release rate was faster at higher molecular weight of the polymer. Compared with docetaxel solution and docetaxel-loaded liposomes, FA-PDCT-L demonstrated the strongest cytotoxicity against two carcinoma cell lines, the greatest intracellular uptake especially in the nucleus, as well as the most powerful apoptotic efficacy. In pharmacokinetic studies, the area under the plasma concentration-time curve of FA-PDCT-L was increased 3.82 and 6.23 times in comparison with the values for the docetaxel-loaded liposomes and docetaxel solution, respectively. Meanwhile, a lower concentration of docetaxel was observed for FA-PDCT-L in the liver and spleen, and a significantly higher concentration of FA-PDCT-L in tumors suggested that the presence of FA-PEG-PCHL on the liposomes resulted in greater accumulation of the drug in tumor tissue.Conclusion: Liposomes modified by FA-PEG-PCHL could be one of the promising suspensions for the delivery of antitumor drugs in cancer.Keywords: folate-poly (PEG-cyanoacrylate-co-cholesteryl cyanoacrylate), docetaxel, freeze-dried liposomes, tumor targetingLi XTian XZhang JZhao XChen XJiang YWang DPan WDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2011, Iss default, Pp 1167-1184 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Li X Tian X Zhang J Zhao X Chen X Jiang Y Wang D Pan W In vitro and in vivo evaluation of folate receptor-targeting amphiphilic copolymer-modified liposomes loaded with docetaxel
description	Xiang Li1, Xin Tian2, Jing Zhang3, Xu Zhao1, Xiaohui Chen1, Youhong Jiang2, Dongkai Wang1, Weisan Pan11Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang; 2The Second Laboratory of Cancer Research Institution, The First Hospital of China Medical University, Shenyang; 3Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, ChinaBackground: The purpose of this study was to develop folate-poly (PEG-cyanoacrylate-co-cholesteryl cyanoacrylate) (FA-PEG-PCHL)-modified freeze-dried liposomes for targeted chemotherapy using docetaxel as a model drug.Methods: FA-PEG-PCHL was synthesized and its cytotoxicity was evaluated by CCK-8 assay in L929. Docetaxel-loaded liposomes modified by FA-PEG-PCHL were prepared by an organic solvent injection method and lyophilized to obtain freeze-dried FA-PEG-PCHL-docetaxel liposomes (FA-PDCT-L). Two carcinoma cell lines (MCF-7 and A-549 cells) were cultured with docetaxel solution, conventional docetaxel-loaded liposomes, or FA-PDCT-L, and the cytotoxicity and apoptosis was evaluated for each preparation. The uptake of the docetaxel preparations into MCF-7 cells was studied by confocal laser scanning microscopy. Liquid chromatography-mass spectrometry was used to study the pharmacokinetics and tissue distribution characteristics of the preparations.Results: The existence of an enlarged fixed aqueous layer on the surface of the liposomes was affirmed by zeta potential analysis. The entrapment efficiency and particle size distribution were almost the same as those of docetaxel-loaded liposomes. The drug release profile showed that the release rate was faster at higher molecular weight of the polymer. Compared with docetaxel solution and docetaxel-loaded liposomes, FA-PDCT-L demonstrated the strongest cytotoxicity against two carcinoma cell lines, the greatest intracellular uptake especially in the nucleus, as well as the most powerful apoptotic efficacy. In pharmacokinetic studies, the area under the plasma concentration-time curve of FA-PDCT-L was increased 3.82 and 6.23 times in comparison with the values for the docetaxel-loaded liposomes and docetaxel solution, respectively. Meanwhile, a lower concentration of docetaxel was observed for FA-PDCT-L in the liver and spleen, and a significantly higher concentration of FA-PDCT-L in tumors suggested that the presence of FA-PEG-PCHL on the liposomes resulted in greater accumulation of the drug in tumor tissue.Conclusion: Liposomes modified by FA-PEG-PCHL could be one of the promising suspensions for the delivery of antitumor drugs in cancer.Keywords: folate-poly (PEG-cyanoacrylate-co-cholesteryl cyanoacrylate), docetaxel, freeze-dried liposomes, tumor targeting
format	article
author	Li X Tian X Zhang J Zhao X Chen X Jiang Y Wang D Pan W
author_facet	Li X Tian X Zhang J Zhao X Chen X Jiang Y Wang D Pan W
author_sort	Li X
title	In vitro and in vivo evaluation of folate receptor-targeting amphiphilic copolymer-modified liposomes loaded with docetaxel
title_short	In vitro and in vivo evaluation of folate receptor-targeting amphiphilic copolymer-modified liposomes loaded with docetaxel
title_full	In vitro and in vivo evaluation of folate receptor-targeting amphiphilic copolymer-modified liposomes loaded with docetaxel
title_fullStr	In vitro and in vivo evaluation of folate receptor-targeting amphiphilic copolymer-modified liposomes loaded with docetaxel
title_full_unstemmed	In vitro and in vivo evaluation of folate receptor-targeting amphiphilic copolymer-modified liposomes loaded with docetaxel
title_sort	in vitro and in vivo evaluation of folate receptor-targeting amphiphilic copolymer-modified liposomes loaded with docetaxel
publisher	Dove Medical Press
publishDate	2011
url	https://doaj.org/article/959df920be3a4433ae892ff26b390fd4
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In vitro and in vivo evaluation of folate receptor-targeting amphiphilic copolymer-modified liposomes loaded with docetaxel

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