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用于药物靶向的固体脂质纳米粒上血浆蛋白的吸附动力学

Adsorption kinetics of plasma proteins on solid lipid nanoparticles for drug targeting.

作者信息

Göppert T M, Müller R H

机构信息

The Free University of Berlin, Institute of Pharmacy, Department of Pharmaceutical Technology, Biotechnology and Quality Management, Kelchstr. 31, 12169 Berlin, Germany.

出版信息

Int J Pharm. 2005 Sep 30;302(1-2):172-86. doi: 10.1016/j.ijpharm.2005.06.025.


DOI:10.1016/j.ijpharm.2005.06.025
PMID:16098695
Abstract

The interactions of intravenously injected carriers with plasma proteins are the determining factor for the in vivo fate of the particles. In this study the adsorption kinetics on solid lipid nanoparticles (SLN) were investigated and compared to the adsorption kinetics on previously analyzed polymeric model particles and O/W-emulsions. The adsorbed proteins were determined using two-dimensional polyacrylamide gel electrophoresis (2-DE). Employing diluted human plasma, a transient adsorption of fibrinogen was observed on the surface of SLN stabilized with the surfactant Tego Care 450, which in plasma of higher concentrations was displaced by apolipoproteins. This was in agreement with the "Vroman-effect" previously determined on solid surfaces. It says that in the early stages of adsorption, more plentiful proteins with low affinity are displaced by less plentiful with higher affinity to the surface. Over a period of time (0.5 min to 4 h) more interesting for the organ distribution of long circulating carriers, no relevant changes in the composition of the adsorption patterns of SLN, surface-modified with poloxamine 908 and poloxamer 407, respectively, were detected. This is in contrast to the chemically similar surface-modified polymeric particles but well in agreement with the surface-modified O/W-emulsions. As there is no competitive displacement of apolipoproteins on these modified SLN, the stable adsorption patterns may be better exploited for drug targeting than particles with an adsorption pattern being very dependent on contact time with plasma.

摘要

静脉注射载体与血浆蛋白的相互作用是颗粒在体内命运的决定性因素。在本研究中,研究了固体脂质纳米粒(SLN)的吸附动力学,并与先前分析的聚合物模型颗粒和O/W乳液的吸附动力学进行了比较。使用二维聚丙烯酰胺凝胶电泳(2-DE)测定吸附的蛋白质。使用稀释的人血浆,观察到纤维蛋白原在由表面活性剂Tego Care 450稳定的SLN表面上的瞬时吸附,在较高浓度的血浆中,它被载脂蛋白取代。这与先前在固体表面上确定的“Vroman效应”一致。它表明在吸附的早期阶段,低亲和力的更丰富蛋白质被对表面具有更高亲和力的较不丰富蛋白质所取代。在对于长循环载体的器官分布更感兴趣的一段时间内(0.5分钟至4小时),分别用泊洛沙明908和泊洛沙姆407进行表面改性的SLN的吸附模式组成没有检测到相关变化。这与化学性质相似的表面改性聚合物颗粒形成对比,但与表面改性的O/W乳液一致。由于在这些改性的SLN上没有载脂蛋白的竞争性置换,与吸附模式非常依赖于与血浆接触时间的颗粒相比,稳定的吸附模式可能更有利于药物靶向。

相似文献

[1]
Adsorption kinetics of plasma proteins on solid lipid nanoparticles for drug targeting.

Int J Pharm. 2005-9-30

[2]
Protein adsorption patterns on poloxamer- and poloxamine-stabilized solid lipid nanoparticles (SLN).

Eur J Pharm Biopharm. 2005-8

[3]
Plasma protein adsorption of Tween 80- and poloxamer 188-stabilized solid lipid nanoparticles.

J Drug Target. 2003-5

[4]
Identification of plasma proteins facilitated by enrichment on particulate surfaces: analysis by two-dimensional electrophoresis and N-terminal microsequencing.

Electrophoresis. 1997-12

[5]
Alternative sample preparation prior to two-dimensional electrophoresis protein analysis on solid lipid nanoparticles.

Electrophoresis. 2004-1

[6]
Adsorption kinetics of plasma proteins on ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles.

Int J Pharm. 2012-2-8

[7]
Plasma protein adsorption patterns on emulsions for parenteral administration: establishment of a protocol for two-dimensional polyacrylamide electrophoresis.

Electrophoresis. 1998-2

[8]
Plasma protein adsorption patterns on liposomes: establishment of analytical procedure.

Electrophoresis. 1996-3

[9]
Investigation of surface-modified solid lipid nanocontainers formulated with a heterolipid-templated homolipid.

Int J Pharm. 2007-4-4

[10]
In vitro adsorption of plasma proteins onto the surface (charges) modified-submicron emulsions for intravenous administration.

Eur J Pharm Biopharm. 2005-1

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