Department for Micro- and Nanotechnology, Technical University of Denmark, Building 345C, 2800 Kgs. Lyngby, Denmark.
Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark.
Int J Pharm. 2017 Apr 30;522(1-2):90-97. doi: 10.1016/j.ijpharm.2017.03.003. Epub 2017 Mar 4.
The diffusion dynamics of nanocarriers in the vitreous and the influence of nanocarrier physicochemical properties on these dynamics is an important aspect of the efficacy of intravitreal administered nanomedicines for the treatment of posterior segment eye diseases. Here we use fluorescence correlation spectroscopy (FCS) to determine liposome diffusion coefficients in the intact vitreous (D) of ex vivo porcine eyes using a modified Miyake-Apple technique to minimize the disruption of the vitreous fine structure. We chose to investigate whether the zeta potential of polyethylene glycol functionalized (i.e. PEGylated) liposomes altered liposome in situ diffusion dynamics in the vitreous. Non-PEGylated cationic nanocarriers have previously shown little to no diffusion in the vitreous, whilst neutral and anionic have shown diffusion. The liposomes investigated had diameters below 150nm and zeta potentials ranging from -20 to +12mV. We observed that PEGylated cationic liposomes had significantly lower D values (1.14μms) than PEGylated neutral and anionic liposomes (2.78 and 2.87μms). However, PEGylated cationic liposomes had a similar biodistribution profile across the vitreous to the other systems. These results show that PEGylated cationic liposomes with limited cationic charge can diffuse across the vitreous and indicate that the vitreous as a barrier to nanocarriers (Ø<500nm) is more complicated than simply an electrostatic barrier as previously suggested.
纳米载体在玻璃体内的扩散动力学以及纳米载体理化性质对这些动力学的影响是玻璃体内给药的纳米药物治疗后节段眼病疗效的一个重要方面。在这里，我们使用荧光相关光谱（FCS）来确定使用 Miyake-Apple 技术（以最小化玻璃体精细结构的破坏）修饰后的离体猪眼玻璃体（D）中脂质体的扩散系数。我们选择研究聚乙二醇（即 PEG）功能化的脂质体的 ζ 电位是否改变了脂质体在玻璃体中的原位扩散动力学。先前的研究表明，非 PEG 化的阳离子纳米载体在玻璃体内几乎没有扩散，而中性和阴离子则有扩散。研究的脂质体直径小于 150nm，ζ 电位范围为-20 至+12mV。我们观察到，PEG 化阳离子脂质体的 D 值（1.14μm/s）明显低于 PEG 化中性和阴离子脂质体（2.78 和 2.87μm/s）。然而，PEG 化阳离子脂质体在玻璃体内的分布与其他系统相似。这些结果表明，具有有限正电荷的 PEG 化阳离子脂质体可以扩散穿过玻璃体，表明玻璃体作为纳米载体的屏障（Ø<500nm）比之前认为的仅仅是静电屏障更为复杂。
