Veliskova Martina, Zvarik Milan, Suty Simon, Jacko Juraj, Mydla Patrick, Cechova Katarina, Dzubinska Daniela, Morvova Marcela, Ionov Maksim, Terehova Maria, Majoral Jean-Pierre, Bryszewska Maria, Waczulikova Iveta
Department of Nuclear Physics and Biophysics, Faculty of Mathematics, Physics and Informatics, Comenius University, Mlynska Dolina F1, 84248 Bratislava, Slovakia.
Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska St., 90-236 Lodz, Poland.
Pharmaceutics. 2022 Jul 30;14(8):1596. doi: 10.3390/pharmaceutics14081596.
Drug delivery by dendron-based nanoparticles is widely studied due to their ability to encapsulate or bind different ligands. For medical purposes, it is necessary (even if not sufficient) for these nanostructures to be compatible with blood. We studied the interaction of amphiphilic dendrons with blood samples from healthy volunteers using standard laboratory methods and rheological measurements. We did not observe clinically relevant abnormalities, but we found a concentration-dependent increase in whole blood viscosity, higher in males, presumably due to the formation of aggregates. To characterize the nature of the interactions among blood components and dendrons, we performed experiments on the liposomes and exosomes as models of biological membranes. Based on results obtained using diverse biophysical methods, we conclude that the interactions were of electrostatic nature. Overall, we have confirmed a concentration-dependent effect of dendrons on membrane systems, while the effect of generation was ambiguous. At higher dendron concentrations, the structure of membranes became disturbed, and membranes were prone to forming bigger aggregates, as visualized by SEM. This might have implications for blood flow disturbances when used in vivo. We propose to introduce blood viscosity measurements in early stages of investigation as they can help to optimize drug-like properties of potential drug carriers.
基于树枝状大分子的纳米颗粒给药因其能够封装或结合不同配体而得到广泛研究。出于医学目的,这些纳米结构与血液相容是必要的(即使不充分)。我们使用标准实验室方法和流变学测量研究了两亲性树枝状大分子与健康志愿者血液样本的相互作用。我们未观察到临床相关异常,但发现全血粘度呈浓度依赖性增加,男性中更高,推测是由于聚集体的形成。为了表征血液成分与树枝状大分子之间相互作用的性质,我们以脂质体和外泌体作为生物膜模型进行了实验。基于使用多种生物物理方法获得的结果,我们得出相互作用是静电性质的结论。总体而言,我们证实了树枝状大分子对膜系统具有浓度依赖性效应,而代数的影响不明确。在较高的树枝状大分子浓度下,膜结构受到干扰,膜易于形成更大的聚集体,如扫描电子显微镜所见。这在体内使用时可能对血流紊乱有影响。我们建议在研究早期引入血液粘度测量,因为它们有助于优化潜在药物载体的类药物性质。