Institute of Organic Chemistry, Johannes Gutenberg-University Mainz , Duesbergweg 10-14, D-55099 Mainz, Germany.
Biomacromolecules. 2014 Apr 14;15(4):1526-33. doi: 10.1021/bm500199h. Epub 2014 Apr 3.
For systemic siRNA delivery applications, well-defined drug carriers are required that guarantee stability for both carrier and cargo. Among various concepts progressing in market or final development, cationic nanohydrogel particles may serve as novel transport media especially designed for siRNA-in vivo experiments. In this work, the interaction of nanohydrogel particles with proteins and serum components was studied via dynamic light scattering in human blood serum as novel screening method prior to applications in vivo. The formation of larger aggregates mostly caused by charge interaction with albumin could be suppressed by nanogel loading with siRNA affording a neutral zeta potential for the complex. Preliminary in vivo studies confirmed the results inside the light-scattering cuvette. Although both carrier and cargo may have limited stability on their own under physiological relevant conditions, they can form safe and stable complexes at a charge neutralized ratio and thus making them applicable to systemic siRNA delivery.
对于系统性 siRNA 递药应用，需要使用具有良好定义的药物载体，以保证载体和货物的稳定性。在市场上或最终开发中出现的各种概念中，阳离子纳米水凝胶颗粒可用作新型的输送介质，专门设计用于 siRNA 的体内实验。在这项工作中，通过动态光散射研究了纳米水凝胶颗粒与人血清中的蛋白质和血清成分的相互作用，作为体内应用之前的新型筛选方法。通过用 siRNA 负载纳米凝胶，可以抑制主要由与白蛋白的电荷相互作用引起的更大的聚集物的形成，从而为复合物提供中性的 Zeta 电位。初步的体内研究证实了在光散射比色皿中的结果。尽管载体和货物本身在生理相关条件下可能具有有限的稳定性，但它们可以在电荷中和的比例下形成安全稳定的复合物，从而使它们适用于系统性 siRNA 递药。
