Preparation, characterization and systemic application of self-assembled hydroxyethyl starch nanoparticles-loaded flavonoid Morin for hyperuricemia therapy

Jianbo Li,1 Yang Yang,1 Likang Lu,2 Qiujin Ma,2 Jinjie Zhang2 1Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, People’s Republic of China; 2School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, People’s Republic of China Backgrou...

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Autores principales:	Li J, Yang Y, Lu L, Ma Q, Zhang J
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	HES-DOCA drug loading efficiency antihyperuricemic activities half-life Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/7d2fb5609c824da99269a5757d9756a3
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spelling	oai:doaj.org-article:7d2fb5609c824da99269a5757d9756a32021-12-02T02:24:24ZPreparation, characterization and systemic application of self-assembled hydroxyethyl starch nanoparticles-loaded flavonoid Morin for hyperuricemia therapy1178-2013https://doaj.org/article/7d2fb5609c824da99269a5757d9756a32018-04-01T00:00:00Zhttps://www.dovepress.com/preparation-characterization-and-systemic-application-of-self-assemble-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Jianbo Li,1 Yang Yang,1 Likang Lu,2 Qiujin Ma,2 Jinjie Zhang2 1Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, People’s Republic of China; 2School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, People’s Republic of China Background: Morin, one of the most widely distributed flavonoids in plants, has been identified as a potent antihyperuricemic agent. Its poor water solubility and fast in vivo clearance, however, have limited its application in the treatment of hyperuricemia. In this study, a novel amphiphilic polymer (hydroxyethyl starch-deoxycholic acid [HES-DOCA]) was synthesized to overcome these limitations.Methods: HES-DOCA conjugates with various substitution degrees were prepared by chemical grafting DOCA to HES through ester formation. The structures of the conjugates were confirmed by infrared spectroscopy and 1H-NMR. Physicochemical characterizations of HES-DOCA nanoparticles-loaded Morin (Morin/HES-DOCA-NPs) were studied using dynamic light scattering and transmission electron microscopy (TEM). In vitro release studies were performed to evaluate the release properties of Morin from the NPs. Subsequently, in vivo pharmacokinetic parameters of Morin/HES-DOCA-NPs were investigated in Wistar rats through intravenous administration (2 mg/kg, equivalent to Morin). Antihyperuricemic efficacy of the NPs was evaluated in a rat hyperuricemic model.Results: The optimized HES-based amphiphilic polymer contained approximately 10 DOCA groups per 100 anhydroglucose units of HES, which can spontaneously self-assemble to form spherical NPs as demonstrated by TEM images. Morin/HES-DOCA-NPs were monodispersed (polydispersity index = 0.05) with a mean diameter of 197 nm and exhibited a zeta potential of -14 mV. The use of DOCA as the polymer’s hydrophobic segment enabled high drug loading efficiency (15.6%). After systemic administration, Morin/HES-DOCA-NPs exhibited significantly longer half-life and higher systemic exposure (elimination half-life and area under the plasma concentration–time curve) compared with free drug Morin. In a rat hyperuricemic model, treatment with Morin/HES-DOCA-NPs demonstrated superior therapeutic efficacy over Morin in decreasing serum uric acid level, increasing the uricosuric action, as well as attenuating hyperuricemia-associated inflammation in kidney of rats.Conclusion: Collectively, these findings suggest that the novel HES-based NP formulation of Morin may have great potential for clinical treatment of hyperuricemia. Keywords: HES-DOCA, drug loading efficiency, antihyperuricemic activities, half-life Li JYang YLu LMa QZhang JDove Medical PressarticleHES-DOCAdrug loading efficiencyantihyperuricemic activitieshalf-lifeMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 2129-2141 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	HES-DOCA drug loading efficiency antihyperuricemic activities half-life Medicine (General) R5-920
spellingShingle	HES-DOCA drug loading efficiency antihyperuricemic activities half-life Medicine (General) R5-920 Li J Yang Y Lu L Ma Q Zhang J Preparation, characterization and systemic application of self-assembled hydroxyethyl starch nanoparticles-loaded flavonoid Morin for hyperuricemia therapy
description	Jianbo Li,1 Yang Yang,1 Likang Lu,2 Qiujin Ma,2 Jinjie Zhang2 1Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, People’s Republic of China; 2School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, People’s Republic of China Background: Morin, one of the most widely distributed flavonoids in plants, has been identified as a potent antihyperuricemic agent. Its poor water solubility and fast in vivo clearance, however, have limited its application in the treatment of hyperuricemia. In this study, a novel amphiphilic polymer (hydroxyethyl starch-deoxycholic acid [HES-DOCA]) was synthesized to overcome these limitations.Methods: HES-DOCA conjugates with various substitution degrees were prepared by chemical grafting DOCA to HES through ester formation. The structures of the conjugates were confirmed by infrared spectroscopy and 1H-NMR. Physicochemical characterizations of HES-DOCA nanoparticles-loaded Morin (Morin/HES-DOCA-NPs) were studied using dynamic light scattering and transmission electron microscopy (TEM). In vitro release studies were performed to evaluate the release properties of Morin from the NPs. Subsequently, in vivo pharmacokinetic parameters of Morin/HES-DOCA-NPs were investigated in Wistar rats through intravenous administration (2 mg/kg, equivalent to Morin). Antihyperuricemic efficacy of the NPs was evaluated in a rat hyperuricemic model.Results: The optimized HES-based amphiphilic polymer contained approximately 10 DOCA groups per 100 anhydroglucose units of HES, which can spontaneously self-assemble to form spherical NPs as demonstrated by TEM images. Morin/HES-DOCA-NPs were monodispersed (polydispersity index = 0.05) with a mean diameter of 197 nm and exhibited a zeta potential of -14 mV. The use of DOCA as the polymer’s hydrophobic segment enabled high drug loading efficiency (15.6%). After systemic administration, Morin/HES-DOCA-NPs exhibited significantly longer half-life and higher systemic exposure (elimination half-life and area under the plasma concentration–time curve) compared with free drug Morin. In a rat hyperuricemic model, treatment with Morin/HES-DOCA-NPs demonstrated superior therapeutic efficacy over Morin in decreasing serum uric acid level, increasing the uricosuric action, as well as attenuating hyperuricemia-associated inflammation in kidney of rats.Conclusion: Collectively, these findings suggest that the novel HES-based NP formulation of Morin may have great potential for clinical treatment of hyperuricemia. Keywords: HES-DOCA, drug loading efficiency, antihyperuricemic activities, half-life
format	article
author	Li J Yang Y Lu L Ma Q Zhang J
author_facet	Li J Yang Y Lu L Ma Q Zhang J
author_sort	Li J
title	Preparation, characterization and systemic application of self-assembled hydroxyethyl starch nanoparticles-loaded flavonoid Morin for hyperuricemia therapy
title_short	Preparation, characterization and systemic application of self-assembled hydroxyethyl starch nanoparticles-loaded flavonoid Morin for hyperuricemia therapy
title_full	Preparation, characterization and systemic application of self-assembled hydroxyethyl starch nanoparticles-loaded flavonoid Morin for hyperuricemia therapy
title_fullStr	Preparation, characterization and systemic application of self-assembled hydroxyethyl starch nanoparticles-loaded flavonoid Morin for hyperuricemia therapy
title_full_unstemmed	Preparation, characterization and systemic application of self-assembled hydroxyethyl starch nanoparticles-loaded flavonoid Morin for hyperuricemia therapy
title_sort	preparation, characterization and systemic application of self-assembled hydroxyethyl starch nanoparticles-loaded flavonoid morin for hyperuricemia therapy
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/7d2fb5609c824da99269a5757d9756a3
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Preparation, characterization and systemic application of self-assembled hydroxyethyl starch nanoparticles-loaded flavonoid Morin for hyperuricemia therapy

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