Blood Compatibility of Amphiphilic Phosphorous Dendrons—Prospective Drug Nanocarriers

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 int...

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Autores principales:	Simon Suty, Veronika Oravczova, Zuzana Garaiova, Veronika Subjakova, Maksim Ionov, Dzmitry Shcharbin, Zuzana Simonikova, Peter Bartek, Milan Zvarik, Xiangyang Shi, Serge Mignani, Jean-Pierre Majoral, Maria Bryszewska, Tibor Hianik, Iveta Waczulikova
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	nanoparticles amphiphilic dendrons blood compatibility liposomes Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/cd2b0dd4cd654d82bd4706b1df56a338
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spelling	oai:doaj.org-article:cd2b0dd4cd654d82bd4706b1df56a3382021-11-25T16:50:37ZBlood Compatibility of Amphiphilic Phosphorous Dendrons—Prospective Drug Nanocarriers10.3390/biomedicines91116722227-9059https://doaj.org/article/cd2b0dd4cd654d82bd4706b1df56a3382021-11-01T00:00:00Zhttps://www.mdpi.com/2227-9059/9/11/1672https://doaj.org/toc/2227-9059Dendrons 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.Simon SutyVeronika OravczovaZuzana GaraiovaVeronika SubjakovaMaksim IonovDzmitry ShcharbinZuzana SimonikovaPeter BartekMilan ZvarikXiangyang ShiSerge MignaniJean-Pierre MajoralMaria BryszewskaTibor HianikIveta WaczulikovaMDPI AGarticlenanoparticlesamphiphilic dendronsblood compatibilityliposomesBiology (General)QH301-705.5ENBiomedicines, Vol 9, Iss 1672, p 1672 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	nanoparticles amphiphilic dendrons blood compatibility liposomes Biology (General) QH301-705.5
spellingShingle	nanoparticles amphiphilic dendrons blood compatibility liposomes Biology (General) QH301-705.5 Simon Suty Veronika Oravczova Zuzana Garaiova Veronika Subjakova Maksim Ionov Dzmitry Shcharbin Zuzana Simonikova Peter Bartek Milan Zvarik Xiangyang Shi Serge Mignani Jean-Pierre Majoral Maria Bryszewska Tibor Hianik Iveta Waczulikova Blood Compatibility of Amphiphilic Phosphorous Dendrons—Prospective Drug Nanocarriers
description	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.
format	article
author	Simon Suty Veronika Oravczova Zuzana Garaiova Veronika Subjakova Maksim Ionov Dzmitry Shcharbin Zuzana Simonikova Peter Bartek Milan Zvarik Xiangyang Shi Serge Mignani Jean-Pierre Majoral Maria Bryszewska Tibor Hianik Iveta Waczulikova
author_facet	Simon Suty Veronika Oravczova Zuzana Garaiova Veronika Subjakova Maksim Ionov Dzmitry Shcharbin Zuzana Simonikova Peter Bartek Milan Zvarik Xiangyang Shi Serge Mignani Jean-Pierre Majoral Maria Bryszewska Tibor Hianik Iveta Waczulikova
author_sort	Simon Suty
title	Blood Compatibility of Amphiphilic Phosphorous Dendrons—Prospective Drug Nanocarriers
title_short	Blood Compatibility of Amphiphilic Phosphorous Dendrons—Prospective Drug Nanocarriers
title_full	Blood Compatibility of Amphiphilic Phosphorous Dendrons—Prospective Drug Nanocarriers
title_fullStr	Blood Compatibility of Amphiphilic Phosphorous Dendrons—Prospective Drug Nanocarriers
title_full_unstemmed	Blood Compatibility of Amphiphilic Phosphorous Dendrons—Prospective Drug Nanocarriers
title_sort	blood compatibility of amphiphilic phosphorous dendrons—prospective drug nanocarriers
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/cd2b0dd4cd654d82bd4706b1df56a338
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Blood Compatibility of Amphiphilic Phosphorous Dendrons—Prospective Drug Nanocarriers

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