Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmacy, Ghent University, Ghent, Belgium.
Biomaterials. 2011 Dec;32(34):9120-7. doi: 10.1016/j.biomaterials.2011.08.015. Epub 2011 Sep 3.
Although the behavior of nanoscopic delivery systems in blood is an important parameter when contemplating their intravenous injection, this aspect is often poorly investigated when advancing from in vitro to in vivo experiments. In this paper, the behavior of siRNA loaded dextran nanogels in human plasma and blood is examined using fluorescence fluctuation spectroscopy, platelet aggregometry, flow cytometry and single particle tracking. Our results show that, in contrast to their negatively charged counterparts, positively charged siRNA loaded dextran nanogels cause platelet aggregation and show increased binding to human blood cells. Although PEGylating the nanogels did not have a significant effect on their interaction with blood cells, single particle tracking revealed that it is necessary to prevent their aggregation in human plasma. We therefore conclude that PEGylated negatively charged dextran nanogels are the most suited for further in vivo studies as they do not aggregate in human plasma and exhibit minimal interactions with blood cells.
尽管纳米递药系统在血液中的行为是考虑其静脉注射时的一个重要参数，但在将体外实验推进到体内实验时，这一方面往往研究不足。在本文中，使用荧光波动光谱法、血小板聚集仪、流式细胞术和单颗粒跟踪技术研究了负载 siRNA 的葡聚糖纳米凝胶在人血浆和血液中的行为。我们的结果表明，与带负电荷的纳米凝胶相反，带正电荷的负载 siRNA 的葡聚糖纳米凝胶会引起血小板聚集，并显示出与人血细胞的结合增加。尽管将纳米凝胶 PEG 化对其与血细胞的相互作用没有显著影响，但单颗粒跟踪揭示了防止它们在人血浆中聚集是必要的。因此，我们得出结论，PEG 化的带负电荷的葡聚糖纳米凝胶最适合进一步的体内研究，因为它们不会在人血浆中聚集，并且与血细胞的相互作用最小。
