Blood Compatibility of Amphiphilic Phosphorous Dendrons—Prospective Drug Nanocarriers

Abstract

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.

Use of soft nanoparticles as delivery agents in anticancer therapy

“…Установлено, что комплексы миРНК с мицеллами, состоящими из полиамидоаминовых дендронов, быстро проникают через клеточную мембрану путем макропиноцитоза и ингибируют до 90% экспрессии целевого белка. Эти результаты позволяют предположить, что разработка гибких наночастиц на основе дендронов в качестве векторов для доставки нуклеиновых кислот в генной терапии может открыть многообещающие перспективы для лечения генетических заболеваний [32,36].…”

Recent advances in PAMAM dendrimer-based CT contrast agents for molecular imaging and theranostics of cancer

“…8 Importantly, appropriate modifications to the surface of the dendrimers can improve their biocompatibility. 9 In addition, the size of the dendrimers can be adjusted through formation of dendrimer nanoclusters, dendrimer nanogels or core–shell tecto dendrimers (CSTDs) as required to meet the timing of imaging needs with controlled excretion behaviour. 10–12…”

In Vitro Interactions of Amphiphilic Phosphorous Dendrons with Liposomes and Exosomes—Implications for Blood Viscosity Changes

“…Dendrimers are branched polymeric globular structures composed of synthetic molecules, dendrons. They are generally accepted as a fourth class of polymers [1,2]. Amphiphilic dendrons consist of a polar/hydrophilic head and a non-polar/hydrophobic tail [3].…”

“…Their size depends on the number of repetition cycles, called generations. Dendrons and dendrimers have raised interest for their potentially efficient way of delivering drugs to cells [1,4]. Drug molecules can be trapped in inner cavities of polymers or chemically conjugated to their surface [1][2][3][4][5].…”

“…Dendrons and dendrimers have raised interest for their potentially efficient way of delivering drugs to cells [1,4]. Drug molecules can be trapped in inner cavities of polymers or chemically conjugated to their surface [1][2][3][4][5]. Furthermore, ligands can be bonded to nanoparticles or intercalated into the structure by covalent linkage with the polymeric backbone [5].…”