Plasma protein adsorption patterns on liposomes: Establishment of analytical procedure
Plasma protein adsorption patterns on liposomes: Establishment of analytical procedure
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DOI：
10.1002/elps.1150170332
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发表时间：
1996-03-01
期刊：
影响因子：
2.9
通讯作者：
Diederichs, JE
中科院分区：
文献类型：
--
作者：
Diederichs, JE
在静脉注射后，胶体药物载体如脂质体、乳剂、聚合物或固体脂质纳米颗粒立即与血浆蛋白相互作用。吸附的血浆蛋白模式取决于载体表面的物理化学特性，被认为是影响载体体内行为的关键因素。了解蛋白质吸附与体内器官分布之间的关系，可以用来获得药物对不同组织的靶向性。具有不同蛋白质吸附模式的载体将与不同的组织特异性受体相互作用，或将被不同的巨噬细胞亚群识别。采用二维聚丙烯酰胺凝胶电泳（2-D PAGE）测定了蛋白质在聚苯乙烯颗粒上的吸附模式。为了将这种分析方法应用于脂质体等可静脉注射的胶体载体，开发了一种新的样品制备方法。用Sepharose 2B柱进行凝胶过滤，分离培养后的血浆脂质体。该技术允许轻度分离，不依赖于洗脱液成分，只根据大小差异。通过使用具有足够高离子强度的洗脱液，可以最大限度地减少脂质体中蛋白质的解吸和凝胶上的吸附。为了评估分离效率，用紫外光谱法测定了每个被洗脱部分中脂质体和血浆的含量。该分离方法首次分析了血浆蛋白在脂质体上的吸附规律。就大小分布而言，凝胶过滤制样似乎对脂质体的稳定性没有影响。
After intervenous (i.v.) injection, colloidal drug carriers such as liposomes, emulsions, polymeric or solid lipid nanoparticles immediately interact with plasma proteins. The adsorbed plasma protein patterns depend on physicochemical characteristics of the carriers' surface and are regarded as a key factor for the in vivo behavior of the carriers. The comprehension of the correlation between protein adsorption and in vivo organ distribution can be utilized to obtain drug targeting to different tissues. Carriers with different protein adsorption patterns will interact with different tissue-specific receptors or will be recognized by different macrophage subpopulations. Two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) was applied to determine the protein adsorption pattern on polystyrene particles as model carriers. To transfer this analytical method to i.v. injectable colloidal carriers such as liposomes, a new sample preparation method was developed. The separation of liposomes from plasma after incubation was achieved by gel filtration using a Sepharose 2B column. This technique allowed a mild separation independent from eluent composition and only according to size differences. Possible protein desorption from the liposomes and adsorption onto the gel were minimized by using an eluent with a sufficiently high ionic strength. To estimate the efficiency of separation, the content of liposomes and plasma in each fraction being eluted was determined by ultraviolet (UV) spectroscopy. With this new separation method plasma protein adsorption patterns on liposomes could be analyzed for the first time. The sample preparation by gel filtration seemed to have no influence on liposome stability as far as size distribution is concerned.