Blood Compatibility of Amphiphilic Phosphorous Dendrons—Prospective Drug Nanocarriers

Simon Suty (1) , Veronika Oravczova (1) , Zuzana Garaiova (1) , Veronika Subjakova (1) , Maksim Ionov (2) , Dzmitry Shcharbin (3) , Zuzana Simonikova (4) , Peter Bartek (4) , Milan Zvarik (1) , Xiangyang Shi (5, 6) , Serge Mignani (5, 7) , Jean-Pierre Majoral (8) , Maria Bryszewska (2) , Tibor Hianik (1) , Iveta Waczulikova (1)

1 Comenius University in Bratislava
2 Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz
3 Institute of Biophysics and Cell Engineering, NASB, Minsk
4 St. Elizabeth Cancer Institute
5 Centro de Química da Madeira
6 CCEB - College of Chemistry, Chemical Engineering and Biotechnology, Donghua University
7 LCBPT - UMR 8601 - Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques
8 LCC - Laboratoire de chimie de coordination

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 interaction. Overall, we proved that the low-generation amphiphilic phosphorous dendrons were compatible with blood within the studied concentration range. However, interactions between high-generation dendrons at bulk concentrations above 10 µM and platelets and/or clotting factors cannot be excluded.

Mots clés: Nanoparticles; Amphiphilic dendrons; Blood compatibility; Liposomes

Domaines: Polymères; Chimie thérapeutique; Sciences pharmaceutiques

Simon Suty, Veronika Oravczova, Zuzana Garaiova, Veronika Subjakova, Maksim Ionov, et al.. Blood Compatibility of Amphiphilic Phosphorous Dendrons—Prospective Drug Nanocarriers. Biomedicines, 2021, 9 (11), pp.1672. ⟨10.3390/biomedicines9111672⟩. ⟨hal-03658953⟩