Blood Compatibility of Amphiphilic Phosphorous Dendrons—Prospective Drug Nanocarriers

Biomedicines

Serge Mignani¹  Xiangyang Shi¹  Maksim Ionov²  Maria Bryszewska²  Peter Bartek³  Zuzana Simonikova³  Veronika Oravczova⁴  Simon Suty⁴  Veronika Subjakova⁴  Zuzana Garaiova⁴  Iveta Waczulikova⁴  Milan Zvarik⁴  Tibor Hianik⁴  Dzmitry Shcharbin⁵  Jean-Pierre Majoral⁶ 

[1] CQM—Centro de Química da Madeira, MMRG, Universidade da Madeira, Campus da Penteada, 9020-105 Funchal, Portugal;Department of General Biophysics, Faculty of Biology and Environmental protection, University of Lodz, 141/143 Pomorska St., 90-236 Lodz, Poland;Department of Hematology and Transfusiology, St. Elizabeth Cancer Institute, Heydukova 10, 81250 Bratislava, Slovakia;Department of Nuclear Physics and Biophysics, Faculty of Mathematics, Physics and Informatics, Comenius University, Mlynska Dolina F1, 84248 Bratislava, Slovakia;Institute of Biophysics and Cell Engineering, National Academy of Sciences of Belarus (IBCENASB), Akademicheskaya 27, 220072 Minsk, Belarus;Laboratoire de Chimie de Coordination du CNRS, 205 Route de Narbonne, CEDEX 4, 31077 Toulouse, France;

关键词: nanoparticles;    amphiphilic dendrons;    blood compatibility;    liposomes;   

DOI  :  10.3390/biomedicines9111672

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown