Polyelectrolyte layer-by-layer assembled lipid nanoparticles for improving oral absorption of doxorubicin

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	Polyelectrolyte layer-by-layer assembled lipid nanoparticles for improving oral absorption of doxorubicin
	Shen Aijun1 ; Xia Dengning 2; Gan Yong2 ; Li Juan 1
刊名	Acta Pharmaceutica Sinica
	2016
卷号	51 期号:7 页码:1136-1143
关键词	doxorubicin polyelectrolyte layer-by-layer lipid nanoparticle oral absorption
ISSN号	0513-4870
其他题名	聚合物电解质层层组装脂质纳米粒提高多柔比星的口服吸收
文献子类	Article
英文摘要	Polyelectrolyte layer-by-layer assembled lipid nanoparticles (NPs) were prepared to improve their stability against lipolysis in gastrointestinal tract, and efficiency of oral absorption of doxorubicin (DOX). The lipid NPs were prepared by hot melt-probe sonication method. The polyelectrolyte layer-by-layer assembled lipid NPs (DOX-NPs/CS/gamma-PGA) was prepared by layer-by-layer self-assembling polyelectrolytes cationic chitosan (CS) and anionic poly (gamma-glutamic acid) (gamma-PGA) on the surface of lipid NPs based on electrostatic interaction. The particle size, polydispersity index (PDI) and zeta potential of lipid NPs and DOX-NPs/CS/gamma-PGA were determined by dynamic light scattering (DLS). The in vitro drug release was determined in pH 1.2 HCl solution and pH 6.8 phosphate buffer solution (PBS). The stability of lipid NPs against lipolysis was evaluated in simulated gastrointestinal medium containing lipase. The cellular uptake of lipid NPs and DOX-NPs/CS/gamma-PGA was evaluated in Caco-2 cell model. The pharmacokinetic of DOX after oral absorption was studied in SD rats. Results showed that the average particle size and zeta potential of DOX-NPs/CS/gamma-PGA were 180.6 5.4 nm and -38.53 0.29 mV, respectively. The DOX-NPs/CS/gamma-PGA effectively slowed down the release of DOX from nanoparticles, and decreased the lipolysis of lipid NPs in simulated gastrointestinal medium. The cell study showed that DOX-loaded lipid NPs and DOX-NPs/CS/ gamma-PGA remarkably enhanced the cell uptake in comparison with DOX solution. The DOX-NPs/CS/gamma-PGA significantly improved oral absorption of DOX compared with DOX-loaded lipid NPs. The C_(max), t_(max) were 0.76 0.25 mug·mL~(-1) and 0.5 h, respectively; AUC_(0-24 h) was 3.02 folds and the relative bioavailability was 302.46% with DOX solution as reference. The stability of lipid NPs against lipolysis and drug release were significantly improved by layer-by-layer assembling, leading to an improved oral absorption.
资助项目	国家自然科学基金资助项目[00000000] ; 上海市2014年"科技创新行动计划"基础研究资助项目[00000000]
WOS研究方向	Pharmacology & Pharmacy (provided by Clarivate Analytics)
语种	中文
CSCD记录号	CSCD:5744510
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/269247]
专题	药物制剂研究中心
作者单位	1.China Pharmaceutical University, Nanjing, Jiangsu 210009, China.; 2.Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
推荐引用方式 GB/T 7714	Shen Aijun,Xia Dengning,Gan Yong,et al. Polyelectrolyte layer-by-layer assembled lipid nanoparticles for improving oral absorption of doxorubicin[J]. Acta Pharmaceutica Sinica,2016,51(7):1136-1143.
APA	Shen Aijun,Xia Dengning,Gan Yong,&Li Juan.(2016).Polyelectrolyte layer-by-layer assembled lipid nanoparticles for improving oral absorption of doxorubicin.Acta Pharmaceutica Sinica,51(7),1136-1143.
MLA	Shen Aijun,et al."Polyelectrolyte layer-by-layer assembled lipid nanoparticles for improving oral absorption of doxorubicin".Acta Pharmaceutica Sinica 51.7(2016):1136-1143.