Blood Compatibility of Amphiphilic Phosphorous Dendrons—Prospective Drug Nanocarriers

作者：Šimon Šutý, Veronika Oravczová, Zuzana Garaiová, Veronika Šubjaková, Максим Йонов, Dzmitry Shcharbin, Zuzana Šimoníková, Péter Bartek, Milan Zvarík, Xiangyang Shi, Serge M. Mignani, Jean‐Pierre Majoral, Maria J Bryszewska, Tibor Hianik, Iveta Waczulı́ková · 发表于：Biomedicines · 年份：2021 · DOI：10.3390/biomedicines9111672 · 被引用次数：6 · 研究领域：Dendrimers and Hyperbranched Polymers、RNA Interference and Gene Delivery、Polymer Surface Interaction Studies

Dendrons are branched synthetic polymers suitable for preparation of nanosized drug delivery systems. Their interactions with biological systems are mainly predetermined by their chemical structure, terminal groups, surface charge, and the number of branched layers (generation). Any new compound intended to be used, alone or in combination, for medical purposes in humans must be compatible with blood. This study combined results from in vitro experiments on human blood and from laboratory experiments designed to assess the effect of amphiphilic phosphorous dendrons on blood components and model membranes, and to examine the presence and nature of interactions leading to a potential safety concern. The changes in hematological and coagulation parameters upon the addition of dendrons in the concentration range of 2-10 µM were monitored. We found that only the combination of higher concentration and higher generation of the dendron affected the selected clinically relevant parameters: it significantly decreased platelet count and plateletcrit, shortened thrombin time, and increased activated partial thromboplastin time. At the same time, occasional small-sized platelet clumps in blood films under the light microscope were observed. We further investigated aggregation propensity of the positively charged dendrons in model conditions using zwitterionic and negatively charged liposomes. The observed changes in size and zeta potential indicated the electrostatic nature of the intera...