Yoo Jin-Wook, Doshi Nishit, Mitragotri Samir
Department of Chemical Engineering, University of California, Santa Barbara, California 93106-5080, USA.
Macromol Rapid Commun. 2010 Jan 18;31(2):142-8. doi: 10.1002/marc.200900592. Epub 2009 Dec 8.
Targeting, internalization, and intracellular trafficking of carriers are key processes in drug delivery to endothelial cells. We synthesized PLGA particles with spherical and elliptical disk geometries and investigated the effect of particle shape on rate of particle endocytosis and their intracellular distribution in endothelial cells. Elliptical disks (aspect ratio of 5) were endocytosed at a slower rate compared to spheres (1.8 µm diameter) of the same volume. However, both particles were eventually internalized and accumulated around the nucleus. We quantified the orientation of elliptical disks and found that disks, on average, oriented tangentially with the nuclear membrane. The non-spherical geometry of elliptical disks brings unique aspects to the kinetics and equilibrium distribution of these particles in cells.
载体的靶向、内化及细胞内运输是药物递送至内皮细胞过程中的关键环节。我们合成了具有球形和椭圆形盘状几何形状的聚乳酸-羟基乙酸共聚物(PLGA)颗粒,并研究了颗粒形状对其在内皮细胞中的内吞速率及其细胞内分布的影响。与相同体积的球体(直径1.8μm)相比,椭圆形盘状物(长宽比为5)的内吞速率较慢。然而,两种颗粒最终都被内化并聚集在细胞核周围。我们对椭圆形盘状物的取向进行了量化,发现这些盘状物平均与核膜呈切向取向。椭圆形盘状物的非球形几何形状为这些颗粒在细胞中的动力学和平衡分布带来了独特之处。