Biodegradable nanoparticles mimicking platelet binding as a targeted and controlled drug delivery system.
Biodegradable nanoparticles mimicking platelet binding as a targeted and controlled drug delivery system.
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DOI：
10.1016/j.ijpharm.2011.11.043
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发表时间：
2012-02-28
影响因子：
5.8
通讯作者：
Nguyen, Kytai T.
中科院分区：
文献类型：
--
作者：
Kona, Soujanya;Dong, Jing-Fei;Liu, Yaling;Tan, Jifu;Nguyen, Kytai T.
本研究的目的是通过模拟血小板的天然结合能力，通过血小板糖蛋白Ib-α（GP Ibα）与受损内皮细胞（EC）的P-选择素和/或内皮下的血管性血友病因子（vWF）的相互作用，开发靶向纳米颗粒作为药物载体，在流体剪切应力下损伤动脉壁。载药的聚（D，L-乳酸-共-乙醇酸）（PLGA）纳米粒使用标准乳液方法配制，并通过碳二亚胺化学与血小板GPIbα的外部组分glycocalicin缀合。内皮细胞的表面包被和细胞摄取研究表明，PLGA纳米粒子与GPIb的共轭显着增加纳米粒子粘附P-选择素和vWF-包被的表面，以及纳米粒子的流体剪切应力下激活的内皮细胞的摄取。此外，纳米颗粒的尺寸和剪切应力对粘附效率的影响，其特征在于通过平行流室的研究。观察到的结合纳米颗粒密度的减少，增加颗粒尺寸和剪切应力也解释通过计算模型。我们的研究结果表明，GPIb-共轭PLGA纳米粒子可以被用作一个有针对性的和控制的药物输送系统在流动条件下在血管损伤的网站。
This research aims to develop targeted nanoparticles as drug carriers to the injured arterial wall under fluid shear stress by mimicking the natural binding ability of platelets via interactions of glycoprotein Ib-alpha (GP Ibα) of platelets with P-selectin of damaged endothelial cells (ECs) and/or with von Willebrand factor (vWF) of the subendothelium. Drug-loaded poly (D, L-lactic-co-glycolic acid) (PLGA) nanoparticles were formulated using a standard emulsion method and conjugated with glycocalicin, the external fraction of platelet GPIbα, via carbodiimide chemistry. Surface-coated and cellular uptake studies in ECs showed that conjugation of PLGA nanoparticles with GPIb significantly increased nanoparticle adhesion to P-selectin- and vWF-coated surfaces as well as nanoparticle uptake by activated ECs under fluid shear stresses. In addition, effects of nanoparticle size and shear stress on adhesion efficiency were characterized through parallel flow chamber studies. The observed decrease in bound nanoparticle density with increased particle sizes and shear stresses is also explained through a computational model. Our results demonstrate that the GPIb-conjugated PLGA nanoparticles can be used as a targeted and controlled drug delivery system under flow conditions at the site of vascular injury.
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影响因子：
14
作者：
Eniola, AO;Hammer, DA
通讯作者：
Hammer, DA
影响因子：
3.8
作者：
Blackwell, JE;Dagia, NM;Goetz, DJ
通讯作者：
Goetz, DJ
影响因子：
3.8
作者：
Dickerson, JB;Blackwell, JE;Goetz, DJ
通讯作者：
Goetz, DJ
影响因子：
3
作者：
Brown DC;Larson RS
通讯作者：
Larson RS
DOI：
10.1023/a:1014006800514
发表时间：
2002-03-01
影响因子：
3.7
作者：
Cascone, MG;Pot, PM;Zhu, ZH
通讯作者：
Zhu, ZH