COLLOIDAL CARRIERS FOR INTRAVENOUS DRUG TARGETING - PLASMA-PROTEIN ADSORPTION PATTERNS ON SURFACE-MODIFIED LATEX-PARTICLES EVALUATED BY 2-DIMENSIONAL POLYACRYLAMIDE-GEL ELECTROPHORESIS
COLLOIDAL CARRIERS FOR INTRAVENOUS DRUG TARGETING - PLASMA-PROTEIN ADSORPTION PATTERNS ON SURFACE-MODIFIED LATEX-PARTICLES EVALUATED BY 2-DIMENSIONAL POLYACRYLAMIDE-GEL ELECTROPHORESIS
复制标题
DOI：
10.1002/elps.11501401214
复制
发表时间：
1993-12-01
期刊：
影响因子：
2.9
通讯作者：
MULLER, RH
中科院分区：
文献类型：
--
作者：
BLUNK, T;HOCHSTRASSER, DF;MULLER, RH
寻求通过胶体载体靶向身体的特定部位以减少药物副作用。血浆蛋白在静脉注射颗粒上的吸附被认为是解释其器官分布的关键因素：总结合蛋白，或者更可能的是，特定蛋白的存在及其构象，预计会影响巨噬细胞的摄取。聚苯乙烯珠，直径为60 nm，被用作模型载体，其表面的差异改性的吸附日益亲水性嵌段共聚物，泊洛沙姆184，188和407。在血浆中孵育后，通过高分辨率二维聚丙烯酰胺凝胶电泳（2-D PAGE）分析包被珠上的蛋白质吸附模式。监测一些代表性蛋白质的行为，包括白蛋白、纤维蛋白原、IgG、因子B和载脂蛋白A-I、A-TV、C-III、E和J。颗粒越疏水，结合蛋白质的总量越大。然而，这种相关性并不适用于所有分析的蛋白质种类，这证明仅观察物理化学数据来预测器官分布是不够的。相反，必须使用2-D PAGE来建立吸附蛋白与载体在体内行为之间的相关性。
Targeting to specific sites of the body via colloidal carriers is sought in order to reduce drug side effects. The adsorption of plasma proteins on intravenously injected particles is regarded as the key factor in explaining their organ distribution: total bound protein, or, more likely, the presence of specific proteins and their conformation, are expected to influence macrophage uptake. Polystyrene beads, 60 nm in diameter, were used as model carriers; their surface was differentially modified by adsorption of increasingly hydrophilic block copolymers, poloxamers 184, 188 and 407. After incubation in plasma, the patterns of protein adsorption onto coated beads were analyzed by high-resolution two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). The behavior of some representative proteins was monitored, including albumin, fibrinogen, IgG, factor B and the apolipoproteins, A-I, A-TV, C-III, E and J. The more hydrophobic the particles, the larger the total amount of bound protein. However, this correlation was not valid for all of the analyzed protein species, which proves that it is insufficient to look only at physicochemical data to predict organ distribution. On the contrary, it is essential to use 2-D PAGE to establish the correlation between adsorbed proteins and carrier behavior in vivo.