Optimized synthesis of glycyrrhetinic acid-modified chitosan 5-fluorouracil nanoparticles and their characteristics

Mingrong Cheng,1,2,* Houxiang Chen,3,* Yong Wang,4,* Hongzhi Xu,5 Bing He,5 Jiang Han,1 Zhiping Zhang1 1Department of General Surgery, 2Department of Endoscopy, Pudong New Area District Zhoupu Hospital, Shanghai, People's Republic of China; 3Zhejiang Huafon Fiber Research Institute, Zhejian...

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Autores principales:	Cheng M, Chen H, Wang Y, Xu H, He B, Han J, Zhang Z
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/e70a9af254cb44c897fa22b48aa81bd9
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spelling	oai:doaj.org-article:e70a9af254cb44c897fa22b48aa81bd92021-12-02T02:44:06ZOptimized synthesis of glycyrrhetinic acid-modified chitosan 5-fluorouracil nanoparticles and their characteristics1178-2013https://doaj.org/article/e70a9af254cb44c897fa22b48aa81bd92014-01-01T00:00:00Zhttp://www.dovepress.com/optimized-synthesis-of-glycyrrhetinic-acid-modified-chitosan-5-fluorou-a15621https://doaj.org/toc/1178-2013 Mingrong Cheng,1,2,* Houxiang Chen,3,* Yong Wang,4,* Hongzhi Xu,5 Bing He,5 Jiang Han,1 Zhiping Zhang1 1Department of General Surgery, 2Department of Endoscopy, Pudong New Area District Zhoupu Hospital, Shanghai, People's Republic of China; 3Zhejiang Huafon Fiber Research Institute, Zhejiang Huafon Spandex Co, Ltd, Wenzhou, People's Republic of China; 4School of Materials Science and Engineering, Wuhan University of Technology, Wuhan, People’s Republic of China; 5Department of General Surgery, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: The nanoparticle drug delivery system, which uses natural or synthetic polymeric material as a carrier to deliver drugs to targeted tissues, has a broad prospect for clinical application for its targeting, slow-release, and biodegradable properties. Here, we used chitosan (CTS) and hepatoma cell-specific binding molecule glycyrrhetinic acid to synthesize glycyrrhetinic acid-modified chitosan (GA-CTS). The synthetic product was confirmed by infrared (IR) spectra and hydrogen-1 nuclear magnetic resonance. The GA-CTS/5-fluorouracil (5-FU) nanoparticles were synthesized by combining GA-CTS and 5-FU and conjugating 5-FU onto the GA-CTS nanomaterial. The central composite design was performed to optimize the preparation process as CTS:tripolyphosphate sodium (TPP) weight ratio =5:1, 5-FU:CTS weight ratio =1:1, TPP concentration =0.05% (w/v), and cross-link time =50 minutes. GA-CTS/5-FU nanoparticles had a mean particle size of 193.7 nm, a polydispersity index of 0.003, a zeta potential of +27.4 mV, and a drug loading of 1.56%. The GA-CTS/5-FU nanoparticle had a protective effect on the drug against plasma degrading enzyme, and provided a sustained release system comprising three distinct phases of quick, steady, and slow release. Our study showed that the peak time, half-life time, mean residence time and area under the curve of GA-CTS/5-FU were longer or more than those of the 5-FU group, but the maximum concentration (Cmax) was lower. We demonstrated that the nanoparticles accumulated in the liver and have significantly inhibited tumor growth in an orthotropic liver cancer mouse model. Keywords: liver cancer, targeted therapy, chemotherapy, pharmacokinetics efficacyCheng MChen HWang YXu HHe BHan JZhang ZDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 695-710 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Cheng M Chen H Wang Y Xu H He B Han J Zhang Z Optimized synthesis of glycyrrhetinic acid-modified chitosan 5-fluorouracil nanoparticles and their characteristics
description	Mingrong Cheng,1,2,* Houxiang Chen,3,* Yong Wang,4,* Hongzhi Xu,5 Bing He,5 Jiang Han,1 Zhiping Zhang1 1Department of General Surgery, 2Department of Endoscopy, Pudong New Area District Zhoupu Hospital, Shanghai, People's Republic of China; 3Zhejiang Huafon Fiber Research Institute, Zhejiang Huafon Spandex Co, Ltd, Wenzhou, People's Republic of China; 4School of Materials Science and Engineering, Wuhan University of Technology, Wuhan, People’s Republic of China; 5Department of General Surgery, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: The nanoparticle drug delivery system, which uses natural or synthetic polymeric material as a carrier to deliver drugs to targeted tissues, has a broad prospect for clinical application for its targeting, slow-release, and biodegradable properties. Here, we used chitosan (CTS) and hepatoma cell-specific binding molecule glycyrrhetinic acid to synthesize glycyrrhetinic acid-modified chitosan (GA-CTS). The synthetic product was confirmed by infrared (IR) spectra and hydrogen-1 nuclear magnetic resonance. The GA-CTS/5-fluorouracil (5-FU) nanoparticles were synthesized by combining GA-CTS and 5-FU and conjugating 5-FU onto the GA-CTS nanomaterial. The central composite design was performed to optimize the preparation process as CTS:tripolyphosphate sodium (TPP) weight ratio =5:1, 5-FU:CTS weight ratio =1:1, TPP concentration =0.05% (w/v), and cross-link time =50 minutes. GA-CTS/5-FU nanoparticles had a mean particle size of 193.7 nm, a polydispersity index of 0.003, a zeta potential of +27.4 mV, and a drug loading of 1.56%. The GA-CTS/5-FU nanoparticle had a protective effect on the drug against plasma degrading enzyme, and provided a sustained release system comprising three distinct phases of quick, steady, and slow release. Our study showed that the peak time, half-life time, mean residence time and area under the curve of GA-CTS/5-FU were longer or more than those of the 5-FU group, but the maximum concentration (Cmax) was lower. We demonstrated that the nanoparticles accumulated in the liver and have significantly inhibited tumor growth in an orthotropic liver cancer mouse model. Keywords: liver cancer, targeted therapy, chemotherapy, pharmacokinetics efficacy
format	article
author	Cheng M Chen H Wang Y Xu H He B Han J Zhang Z
author_facet	Cheng M Chen H Wang Y Xu H He B Han J Zhang Z
author_sort	Cheng M
title	Optimized synthesis of glycyrrhetinic acid-modified chitosan 5-fluorouracil nanoparticles and their characteristics
title_short	Optimized synthesis of glycyrrhetinic acid-modified chitosan 5-fluorouracil nanoparticles and their characteristics
title_full	Optimized synthesis of glycyrrhetinic acid-modified chitosan 5-fluorouracil nanoparticles and their characteristics
title_fullStr	Optimized synthesis of glycyrrhetinic acid-modified chitosan 5-fluorouracil nanoparticles and their characteristics
title_full_unstemmed	Optimized synthesis of glycyrrhetinic acid-modified chitosan 5-fluorouracil nanoparticles and their characteristics
title_sort	optimized synthesis of glycyrrhetinic acid-modified chitosan 5-fluorouracil nanoparticles and their characteristics
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/e70a9af254cb44c897fa22b48aa81bd9
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_version_	1718402196494614528

Optimized synthesis of glycyrrhetinic acid-modified chitosan 5-fluorouracil nanoparticles and their characteristics

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