Nagayama Susumu, Ogawara Ken-ichi, Fukuoka Yoshiko, Higaki Kazutaka, Kimura Toshikiro
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-Naka, Okayama 700-8530, Japan.
Int J Pharm. 2007 Sep 5;342(1-2):215-21. doi: 10.1016/j.ijpharm.2007.04.036. Epub 2007 May 10.
The relationship between the time-dependent change in serum proteins adsorbed on nanoparticles and their disposition to the liver was investigated by employing lecithin-coated polystyrene nanosphere with a size of 50 nm (LNS-50) as a model nanoparticle in rats. The total amount of proteins adsorbed on LNS-50 increased and the qualitative profile of serum proteins adsorbed on LNS-50 changed during the incubation with serum up to 360 min. The liver perfusion study indicated that the hepatic uptake of LNS-50 incubated with serum for 360 min was significantly larger than those of LNS-50 incubated for shorter period. It was suggested that the increase in the hepatic uptake of LNS-50 with the increase in incubation time would be ascribed mainly to the increase in the opsonin-mediated uptake by Kupffer cells. Semi-quantification of major opsonins, complement C3 (C3) and immunoglobulin G (IgG), and in vitro uptake study in primary cultured Kupffer cells demonstrated that the increase in C3 and IgG amounts adsorbed on LNS-50 was directly reflected in the increased disposition of LNS-50 to Kupffer cells. These results indicate that the amounts of opsonins associated on nanoparticles would change over time and this process would be substantially reflected in the alteration of their hepatic disposition characteristics.
通过使用粒径为50 nm的卵磷脂包被聚苯乙烯纳米球（LNS-50）作为大鼠模型纳米颗粒，研究了吸附在纳米颗粒上的血清蛋白随时间的变化与其在肝脏中的分布之间的关系。在与血清孵育长达360分钟的过程中，吸附在LNS-50上的蛋白质总量增加，且吸附在LNS-50上的血清蛋白的定性图谱发生了变化。肝脏灌注研究表明，与血清孵育360分钟的LNS-50的肝脏摄取量明显大于孵育时间较短的LNS-50。提示LNS-50的肝脏摄取量随孵育时间的增加而增加，这主要归因于库普弗细胞介导的调理吞噬作用的增加。主要调理素补体C3（C3）和免疫球蛋白G（IgG）的半定量分析以及原代培养库普弗细胞的体外摄取研究表明，吸附在LNS-50上的C3和IgG量的增加直接反映在LNS-50对库普弗细胞的分布增加上。这些结果表明，纳米颗粒上结合的调理素量会随时间变化，这一过程将在其肝脏分布特征的改变中得到充分体现。
