Hyaluronan-modified core-shell liponanoparticles targeting CD44-positive retinal pigment epithelium cells via intravitreal injection

doi:10.1016/j.biomaterials.2013.04.035

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	Hyaluronan-modified core-shell liponanoparticles targeting CD44-positive retinal pigment epithelium cells via intravitreal injection
	Gan, Li 1; Wang, Jing 1,2; Zhao, Yanan 1,2; Chen, Dan 1; Zhu, Chunliu1 ; Liu, Jianping 2; Gan, Yong1
刊名	BIOMATERIALS
	2013-08
卷号	34 期号:24 页码:5978-5987
关键词	Hyaluronan Core-shell Liponanoparticles EAU RPE targeting
ISSN号	0142-9612
DOI	10.1016/j.biomaterials.2013.04.035
文献子类	Article
英文摘要	Retinal inflammation, a common process of posterior ocular diseases, may lead to severe vision loss or even blindness. Retinal pigment epithelium (RPE) cells are generally considered as the therapeutic target of inflammation pathogenesis. However, the lack of retina-specific distribution for general intravitreous drug delivery systems makes the anti-inflammation treatment inefficient. In the present study, a hyaluronan (HA)-modified core shell liponanoparticles (HA-LCS-NPs) was designed to improve the treatment efficiency by increasing RPE-targeted distribution. Our in vitro RPE cell uptake study showed that a higher HA grafting density (5.8%) and a higher molecular weight (200-400 kDa) modification of HA improved the intracellular uptake of HA-LCS-NPs. In addition, in vivo distribution evaluation in experimental autoimmune uveitis (EAU) rats revealed that HA-LCS-NPs could specifically target RPE cells through the interaction between the CD44 receptor and the HA ligand, while chitosan nanoparticles (CS-NPs) were limited to the vitreous cavity and the core shell liponanoparticles (LCS-NPs) only reached the inner layers of the retina. At 7 d post-injection, approximately 75% of the fluorescence of HA-LCS-NPs still remained in the RPE/choroid. In conclusion, HA-LCS-NPs might present a promising intraocular drug delivery system to achieve RPE-targeted distribution and prolonged intraocular residence. Published by Elsevier Ltd.
资助项目	National Natural Sciences Foundation of China[81102387] ; Natural Sciences Foundation of Shanghai China[11ZR1444700] ; National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program"[2012ZX09301001-001] ; National Basic Research Program of China[2009CB930300]
WOS关键词	EXPERIMENTAL AUTOIMMUNE UVEORETINITIS ; SELF-ASSEMBLED NANOPARTICLES ; MACULAR DEGENERATION ; DRUG-DELIVERY ; CD44-HYALURONAN INTERACTIONS ; POSTERIOR SEGMENT ; MOLECULAR-WEIGHT ; INFLAMMATION ; LIPOSOMES ; BARRIER
WOS研究方向	Engineering ; Materials Science
语种	英语
出版者	ELSEVIER SCI LTD
WOS记录号	WOS:000320430400011
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277529]
专题	药物制剂研究中心
通讯作者	Gan, Yong
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 2.China Pharmaceut Univ, Sch Pharm, Nanjing 210009, Peoples R China
推荐引用方式 GB/T 7714	Gan, Li,Wang, Jing,Zhao, Yanan,et al. Hyaluronan-modified core-shell liponanoparticles targeting CD44-positive retinal pigment epithelium cells via intravitreal injection[J]. BIOMATERIALS,2013,34(24):5978-5987.
APA	Gan, Li.,Wang, Jing.,Zhao, Yanan.,Chen, Dan.,Zhu, Chunliu.,...&Gan, Yong.(2013).Hyaluronan-modified core-shell liponanoparticles targeting CD44-positive retinal pigment epithelium cells via intravitreal injection.BIOMATERIALS,34(24),5978-5987.
MLA	Gan, Li,et al."Hyaluronan-modified core-shell liponanoparticles targeting CD44-positive retinal pigment epithelium cells via intravitreal injection".BIOMATERIALS 34.24(2013):5978-5987.