Preparation and characterization of self-assembled nanoparticles based on low-molecular-weight heparin and stearylamine conjugates for controlled delivery of docetaxel

Dong-Hwan Kim,1 Ubonvan Termsarasab,1 Hyun-Jong Cho,2 In-Soo Yoon,3 Jae-Young Lee,1 Hyun Tae Moon,1 Dae-Duk Kim1 1College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea; 2College of Pharmacy, Kangwon National University, Chuncheon...

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Autores principales:	Kim DH, Termsarasab U, Cho HJ, Yoon IS, Lee JY, Moon HT, Kim DD
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/f96797ea0ab04b7d89fb82a40021599f
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spelling	oai:doaj.org-article:f96797ea0ab04b7d89fb82a40021599f2021-12-02T03:05:25ZPreparation and characterization of self-assembled nanoparticles based on low-molecular-weight heparin and stearylamine conjugates for controlled delivery of docetaxel1178-2013https://doaj.org/article/f96797ea0ab04b7d89fb82a40021599f2014-12-01T00:00:00Zhttp://www.dovepress.com/preparation-and-characterization-of-self-assembled-nanoparticles-based-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 Dong-Hwan Kim,1 Ubonvan Termsarasab,1 Hyun-Jong Cho,2 In-Soo Yoon,3 Jae-Young Lee,1 Hyun Tae Moon,1 Dae-Duk Kim1 1College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea; 2College of Pharmacy, Kangwon National University, Chuncheon, Republic of Korea; 3College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam, Republic of Korea Abstract: Low-molecular-weight heparin (LMWH)–stearylamine (SA) conjugates (LHSA)-based self-assembled nanoparticles were prepared for intravenous delivery of docetaxel (DCT). 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide were used as coupling agents for synthesis of LHSA conjugates. The physicochemical properties, in vitro antitumor efficacy, in vitro cellular uptake efficiency, in vivo antitumor efficacy, and in vivo pharmacokinetics of LHSA nanoparticles were investigated. The LHSA nanoparticles exhibited a spherical shape with a mean diameter of 140–180 nm and a negative surface charge. According to in vitro release and in vivo pharmacokinetic test results, the docetaxel-loaded LHSA5 (LMWH:SA =1:5) nanoparticles exhibited sustained drug release profiles. The blank LHSA nanoparticles demonstrated only an insignificant cytotoxicity in MCF-7 and MDAMB 231 human breast cancer cells; additionally, higher cellular uptake of coumarin 6 (C6) in MCF-7 and MDAMB 231 cells was observed in the LHSA5 nanoparticles group than that in the C6 solution group. The in vivo tumor growth inhibition efficacy of docetaxel-loaded LHSA5 nanoparticles was also significantly higher than the Taxotere®-treated group in the MDAMB 231 tumor-xenografted mouse model. These results indicated that the LHSA5-based nanoparticles could be a promising anticancer drug delivery system. Keywords: amphiphilic polymer, docetaxel, drug delivery, low-molecular-weight heparin, self-assembled nanoparticleKim DHTermsarasab UCho HJYoon ISLee JYMoon HTKim DDDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 5711-5727 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Kim DH Termsarasab U Cho HJ Yoon IS Lee JY Moon HT Kim DD Preparation and characterization of self-assembled nanoparticles based on low-molecular-weight heparin and stearylamine conjugates for controlled delivery of docetaxel
description	Dong-Hwan Kim,1 Ubonvan Termsarasab,1 Hyun-Jong Cho,2 In-Soo Yoon,3 Jae-Young Lee,1 Hyun Tae Moon,1 Dae-Duk Kim1 1College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea; 2College of Pharmacy, Kangwon National University, Chuncheon, Republic of Korea; 3College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam, Republic of Korea Abstract: Low-molecular-weight heparin (LMWH)–stearylamine (SA) conjugates (LHSA)-based self-assembled nanoparticles were prepared for intravenous delivery of docetaxel (DCT). 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide were used as coupling agents for synthesis of LHSA conjugates. The physicochemical properties, in vitro antitumor efficacy, in vitro cellular uptake efficiency, in vivo antitumor efficacy, and in vivo pharmacokinetics of LHSA nanoparticles were investigated. The LHSA nanoparticles exhibited a spherical shape with a mean diameter of 140–180 nm and a negative surface charge. According to in vitro release and in vivo pharmacokinetic test results, the docetaxel-loaded LHSA5 (LMWH:SA =1:5) nanoparticles exhibited sustained drug release profiles. The blank LHSA nanoparticles demonstrated only an insignificant cytotoxicity in MCF-7 and MDAMB 231 human breast cancer cells; additionally, higher cellular uptake of coumarin 6 (C6) in MCF-7 and MDAMB 231 cells was observed in the LHSA5 nanoparticles group than that in the C6 solution group. The in vivo tumor growth inhibition efficacy of docetaxel-loaded LHSA5 nanoparticles was also significantly higher than the Taxotere®-treated group in the MDAMB 231 tumor-xenografted mouse model. These results indicated that the LHSA5-based nanoparticles could be a promising anticancer drug delivery system. Keywords: amphiphilic polymer, docetaxel, drug delivery, low-molecular-weight heparin, self-assembled nanoparticle
format	article
author	Kim DH Termsarasab U Cho HJ Yoon IS Lee JY Moon HT Kim DD
author_facet	Kim DH Termsarasab U Cho HJ Yoon IS Lee JY Moon HT Kim DD
author_sort	Kim DH
title	Preparation and characterization of self-assembled nanoparticles based on low-molecular-weight heparin and stearylamine conjugates for controlled delivery of docetaxel
title_short	Preparation and characterization of self-assembled nanoparticles based on low-molecular-weight heparin and stearylamine conjugates for controlled delivery of docetaxel
title_full	Preparation and characterization of self-assembled nanoparticles based on low-molecular-weight heparin and stearylamine conjugates for controlled delivery of docetaxel
title_fullStr	Preparation and characterization of self-assembled nanoparticles based on low-molecular-weight heparin and stearylamine conjugates for controlled delivery of docetaxel
title_full_unstemmed	Preparation and characterization of self-assembled nanoparticles based on low-molecular-weight heparin and stearylamine conjugates for controlled delivery of docetaxel
title_sort	preparation and characterization of self-assembled nanoparticles based on low-molecular-weight heparin and stearylamine conjugates for controlled delivery of docetaxel
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/f96797ea0ab04b7d89fb82a40021599f
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_version_	1718402018400272384

Preparation and characterization of self-assembled nanoparticles based on low-molecular-weight heparin and stearylamine conjugates for controlled delivery of docetaxel

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