Development of high drug-loading nanomicelles targeting steroids to the brain

Sijia Zheng,1,* Yanqi Xie,1,* Yuan Li,1 Ling Li,1 Ning Tian,1 Wenbo Zhu,2 Guangmei Yan,2 Chuanbin Wu,1 Haiyan Hu1 1School of Pharmaceutical Sciences, 2Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China *These authors contr...

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Autores principales:	Zheng S, Xie Y, Li Y, Li L, Tian N, Zhu W, Yan G, Wu C, Hu H
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/4c94f4124a95461990d415dab064a8ff
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spelling	oai:doaj.org-article:4c94f4124a95461990d415dab064a8ff2021-12-02T02:10:30ZDevelopment of high drug-loading nanomicelles targeting steroids to the brain1178-2013https://doaj.org/article/4c94f4124a95461990d415dab064a8ff2013-12-01T00:00:00Zhttp://www.dovepress.com/development-of-high-drug-loading-nanomicelles-targeting-steroids-to-th-a15320https://doaj.org/toc/1178-2013 Sijia Zheng,1,* Yanqi Xie,1,* Yuan Li,1 Ling Li,1 Ning Tian,1 Wenbo Zhu,2 Guangmei Yan,2 Chuanbin Wu,1 Haiyan Hu1 1School of Pharmaceutical Sciences, 2Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China *These authors contributed equally to this workAbstract: The objective of this research was to develop and evaluate high drug-loading ligand-modified nanomicelles to deliver a steroidal compound to the brain. YC1 (5α-cholestane-24-methylene-3β, 5α, 6β, 19-tetraol), with poor solubility and limited access to the brain, for the first time, has been proved to be an effective neuroprotective steroid by our previous studies. Based on the principle of ‘like dissolves like’, cholesterol, which shares the same steroidal parent nucleus with YC1, was selected to react with sodium alginate, producing amphiphilic sodium alginate–cholesterol derivatives (SACDs). To increase the grafting ratio and drug loading, cholesterol was converted to cholesteryl chloroformate, for the first time, before reacting with sodium alginate. Further, lactoferrin was conjugated on SACDs to provide lactoferrin-SACDs (Lf-SACD), which was established by immune electron microscopy (IEM) and self-assembled into brain-targeting nanomicelles. These nanomicelles were negatively charged and spherical in nature, with an average size of <200 nm. The YC1 drug loading was increased due to the cholesteryl inner cores of the nanomicelles, and the higher the grafting ratio was, the lower the critical micelle concentration (CMC) value of SACD, and the higher drug loading. The in vitro drug release, studied by bulk-equilibrium dialysis in 20 mL of 6% hydroxypropyl-β-cyclodextrin solution at 37°C, indicated a prolonged release profile. The YC1 concentration in mouse brain delivered by lactoferrin-modified nanomicelles was higher than in those delivered by non-modified nanomicelles and YC1 solution. The unique brain-targeting nanomicelle system may provide a promising carrier to deliver hydrophobic drugs across the blood–brain barrier for the treatment of brain diseases.Keywords: drug-loading, lactoferrin, nanomicelles, sodium alginate, cholesterol, brain-targetingZheng SXie YLi YLi LTian NZhu WYan GWu CHu HDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 55-66 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Zheng S Xie Y Li Y Li L Tian N Zhu W Yan G Wu C Hu H Development of high drug-loading nanomicelles targeting steroids to the brain
description	Sijia Zheng,1,* Yanqi Xie,1,* Yuan Li,1 Ling Li,1 Ning Tian,1 Wenbo Zhu,2 Guangmei Yan,2 Chuanbin Wu,1 Haiyan Hu1 1School of Pharmaceutical Sciences, 2Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China *These authors contributed equally to this workAbstract: The objective of this research was to develop and evaluate high drug-loading ligand-modified nanomicelles to deliver a steroidal compound to the brain. YC1 (5α-cholestane-24-methylene-3β, 5α, 6β, 19-tetraol), with poor solubility and limited access to the brain, for the first time, has been proved to be an effective neuroprotective steroid by our previous studies. Based on the principle of ‘like dissolves like’, cholesterol, which shares the same steroidal parent nucleus with YC1, was selected to react with sodium alginate, producing amphiphilic sodium alginate–cholesterol derivatives (SACDs). To increase the grafting ratio and drug loading, cholesterol was converted to cholesteryl chloroformate, for the first time, before reacting with sodium alginate. Further, lactoferrin was conjugated on SACDs to provide lactoferrin-SACDs (Lf-SACD), which was established by immune electron microscopy (IEM) and self-assembled into brain-targeting nanomicelles. These nanomicelles were negatively charged and spherical in nature, with an average size of <200 nm. The YC1 drug loading was increased due to the cholesteryl inner cores of the nanomicelles, and the higher the grafting ratio was, the lower the critical micelle concentration (CMC) value of SACD, and the higher drug loading. The in vitro drug release, studied by bulk-equilibrium dialysis in 20 mL of 6% hydroxypropyl-β-cyclodextrin solution at 37°C, indicated a prolonged release profile. The YC1 concentration in mouse brain delivered by lactoferrin-modified nanomicelles was higher than in those delivered by non-modified nanomicelles and YC1 solution. The unique brain-targeting nanomicelle system may provide a promising carrier to deliver hydrophobic drugs across the blood–brain barrier for the treatment of brain diseases.Keywords: drug-loading, lactoferrin, nanomicelles, sodium alginate, cholesterol, brain-targeting
format	article
author	Zheng S Xie Y Li Y Li L Tian N Zhu W Yan G Wu C Hu H
author_facet	Zheng S Xie Y Li Y Li L Tian N Zhu W Yan G Wu C Hu H
author_sort	Zheng S
title	Development of high drug-loading nanomicelles targeting steroids to the brain
title_short	Development of high drug-loading nanomicelles targeting steroids to the brain
title_full	Development of high drug-loading nanomicelles targeting steroids to the brain
title_fullStr	Development of high drug-loading nanomicelles targeting steroids to the brain
title_full_unstemmed	Development of high drug-loading nanomicelles targeting steroids to the brain
title_sort	development of high drug-loading nanomicelles targeting steroids to the brain
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/4c94f4124a95461990d415dab064a8ff
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Development of high drug-loading nanomicelles targeting steroids to the brain

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