The characteristics and mechanism of simvastatin loaded lipid nanoparticles to increase oral bioavailability in rats

doi:10.1016/j.ijpharm.2010.04.039

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	The characteristics and mechanism of simvastatin loaded lipid nanoparticles to increase oral bioavailability in rats
	Zhang, Zhiwen2 ; Bu, Huihui 2; Gao, Zhiwei2 ; Huang, Yan 2; Gao, Fang 1,2; Li, Yaping2
刊名	INTERNATIONAL JOURNAL OF PHARMACEUTICS
	2010-07-15
卷号	394 期号:1-2 页码:147-153
关键词	Simvastatin Simvastatin acid Lipid nanoparticles Intestinal absorption Bioavailability
ISSN号	0378-5173
DOI	10.1016/j.ijpharm.2010.04.039
文献子类	Article
英文摘要	Simvastatin (SV), a cholesterol-lowering agent, has been widely used in the treatment of hypercholesterolemia, dyslipidemia and coronary heart disease, but SV shows the low oral bioavailability due to its poor aqueous solubility and extensive metabolism by cytochrome-3A system in intestinal guts and liver. In this work. SV loaded lipid nanoparticles (SLNs) with different components were designed to enhance its oral bioavailability, and the plasma concentration of SV and its active metabolite (simvastatin acid, SVA) was determined by LC-MS-MS method. The experimental results showed that SLNs were spherical nano-sized particles with high encapsulation efficiency (>95%). The in situ intestinal absorption indicated that the absorption of SLNs was greatly improved compared with that of free SV, and the absorption was changed with the site of the intestinal segments. SLNs could be uptaken into the enterocytes through both clathrin and caveolae mediated endocytosis pathways. The oral bioavailability of SV after its incorporation into the lipid nanoparticles was improved by 3.37-fold for SLNs I and 2.55-fold for SLNs II compared with that from free SV in rats, and that of the SVA was significantly enhanced as well. As a result, lipid nanoparticles could be a promising delivery system to enhance the oral bioavailability of simvastatin. (C) 2010 Elsevier B.V. All rights reserved.
资助项目	National Basic Research Program of China[2009CB930304] ; National Basic Research Program of China[2007CB935800] ; National Natural Science Foundation of China[30925041] ; National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program"[2009ZX09501-024] ; National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program"[2009ZX09301-001] ; Shanghai Nanomedicine Program[0852nm05700]
WOS关键词	DRUG-DELIVERY SYSTEMS ; POORLY SOLUBLE DRUGS ; IN-VITRO ; FORMULATION ; ABSORPTION ; EXCIPIENTS ; CYTOCHROME-P450 ; ENHANCEMENT ; STRATEGIES
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	ELSEVIER SCIENCE BV
WOS记录号	WOS:000279720400017
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/278834]
专题	药物制剂研究中心
通讯作者	Li, Yaping
作者单位	1.Shenyang Pharmaceut Univ, Sch Pharm, Shenyang 110016, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Delivery Syst, Shanghai 201203, Peoples R China;
推荐引用方式 GB/T 7714	Zhang, Zhiwen,Bu, Huihui,Gao, Zhiwei,et al. The characteristics and mechanism of simvastatin loaded lipid nanoparticles to increase oral bioavailability in rats[J]. INTERNATIONAL JOURNAL OF PHARMACEUTICS,2010,394(1-2):147-153.
APA	Zhang, Zhiwen,Bu, Huihui,Gao, Zhiwei,Huang, Yan,Gao, Fang,&Li, Yaping.(2010).The characteristics and mechanism of simvastatin loaded lipid nanoparticles to increase oral bioavailability in rats.INTERNATIONAL JOURNAL OF PHARMACEUTICS,394(1-2),147-153.
MLA	Zhang, Zhiwen,et al."The characteristics and mechanism of simvastatin loaded lipid nanoparticles to increase oral bioavailability in rats".INTERNATIONAL JOURNAL OF PHARMACEUTICS 394.1-2(2010):147-153.