Jansch M, Jindal A B, Sharmila B Majee, Samad A, Devarajan P V, Müller R H
Department of Pharmaceutics, Biopharmaceutics & NutriCosmetics, Institute of Pharmacy, Freie Universität Berlin, Germany.
Pharmazie. 2013 Jan;68(1):27-33.
The purpose of this study was to evaluate the plasma protein adsorption behavior onto different LIPOMER nanoparticles, especially looking for the first time, if the particle shape affects the protein adsorption pattern. The potential in vivo fate is discussed and compared with previous in vivo animal studies. The two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) was used for identification of adsorbed plasma proteins. Qualitative similar patterns were obtained from the protein adsorption analysis and four apolipoproteins with considerable quantitative differences were identified. Besides the quantitative differences in the adsorbed apolipoproteins, in vitro uptake in the human macrophage cell line U-937 of histocytic lymphoma organ revealed significantly lower uptake of the irregular glycerol monostearate LIPOMER nanoparticles. Therefore, protein adsorption does not seem to play a role in the splenotropic behavior in the sense, that adsorption of opsonins, especially spleen-specific opsonins are required for the uptake. The splenotropic uptake might be favored because all LIPOMER nanoparticles did not adsorb opsonins at all, mediating competitive uptake by liver macrophages. Differences in the in vivo uptake by the spleen were attributed to differences in particle shape with potential super position effect by the quantitative differences in the adsorbed proteins.
本研究的目的是评估血浆蛋白在不同脂质体纳米颗粒上的吸附行为，特别是首次探究颗粒形状是否会影响蛋白吸附模式。讨论了其在体内的潜在命运，并与先前的体内动物研究进行了比较。采用二维聚丙烯酰胺凝胶电泳（2-D PAGE）鉴定吸附的血浆蛋白。从蛋白吸附分析中获得了定性相似的模式，并鉴定出四种载脂蛋白存在显著的定量差异。除了吸附的载脂蛋白存在定量差异外，组织细胞淋巴瘤器官的人巨噬细胞系U-937对不规则单硬脂酸甘油酯脂质体纳米颗粒的体外摄取显著降低。因此，从调理素吸附的意义上来说，蛋白吸附似乎在脾靶向行为中不起作用，即摄取需要调理素的吸附，尤其是脾脏特异性调理素。脾靶向摄取可能更受青睐，因为所有脂质体纳米颗粒根本不吸附调理素，从而介导肝巨噬细胞的竞争性摄取。脾脏体内摄取的差异归因于颗粒形状的差异以及吸附蛋白定量差异可能产生的叠加效应。
