Roser M, Fischer D, Kissel T
Novartis Pharma AG, Basle, Switzerland.
Eur J Pharm Biopharm. 1998 Nov;46(3):255-63. doi: 10.1016/s0939-6411(98)00038-1.
The surface charges on biodegradable albumin nanoparticles were introduced by covalent coupling different primary amines to examine their influence on phagocytosis by macrophages under in vitro conditions. Albumin particles with a zeta potential close to zero showed a reduced phagocytic uptake in comparison with charged particles, especially nanoparticles with a positive zeta potential. The phagocytic uptake in the present study was examined using an established cell culture model based on primary mouse peritoneal macrophages and a human hematopoietic monocytic cell line (U-937) treated with phorbol-12-myristic-13-acetate to induce cell differentiation. The influence of opsonins on in vitro phagocytosis experiments was characterized using carriers pre-treated with human serum. In the presence of human serum the phagocytic activity of U-937 cells was found to be similar to primary mouse macrophages without serum. In contrast to peritoneal macrophages, U-937 cells showed no phagocytic activity in the absence of serum. In particular, only the C3b- complement deposition on the particle surface seems to promote the phagocytic process. The in vivo distribution of albumin carriers in rats was investigated using magnetic resonance imaging (MRI). No differences in blood circulation times and organ accumulation between different nanoparticle preparations with positive, neutral and negative surface charges could be observed in rats, suggesting that the in vivo fate of albumin nanoparticles is significantly influenced by factors not reflected in the in vitro cell culture models.
通过将不同的伯胺共价偶联，引入可生物降解白蛋白纳米颗粒的表面电荷，以研究其在体外条件下对巨噬细胞吞噬作用的影响。与带电颗粒相比，尤其是具有正zeta电位的纳米颗粒，zeta电位接近零的白蛋白颗粒显示出吞噬摄取减少。本研究中的吞噬摄取是使用基于原代小鼠腹腔巨噬细胞和用人佛波醇-12-肉豆蔻酸酯-13-乙酸酯处理以诱导细胞分化的人造血单核细胞系（U-937）建立的细胞培养模型进行检测的。使用用人血清预处理的载体来表征调理素对体外吞噬实验的影响。在人血清存在下，发现U-937细胞的吞噬活性与无血清的原代小鼠巨噬细胞相似。与腹腔巨噬细胞相反，U-937细胞在无血清时无吞噬活性。特别地，似乎只有颗粒表面上的C3b补体沉积促进吞噬过程。使用磁共振成像（MRI）研究了白蛋白载体在大鼠体内的分布。在大鼠中未观察到具有正、中性和负表面电荷的不同纳米颗粒制剂之间在血液循环时间和器官积累方面的差异，这表明白蛋白纳米颗粒的体内命运受到体外细胞培养模型中未反映的因素的显著影响。
