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

Drug delivery by dendron-based nanoparticles is widely studied due to their ability to encapsulate or bind different ligands. For medical purposes, it is necessary (even if not sufficient) for these nanostructures to be compatible with blood. We studied the interaction of amphiphilic dendrons with blood samples from healthy volunteers using standard laboratory methods and rheological measurements. We did not observe clinically relevant abnormalities, but we found a concentration-dependent increase in whole blood viscosity, higher in males, presumably due to the formation of aggregates. To characterize the nature of the interactions among blood components and dendrons, we performed experiments on the liposomes and exosomes as models of biological membranes. Based on results obtained using diverse biophysical methods, we conclude that the interactions were of electrostatic nature. Overall, we have confirmed a concentration-dependent effect of dendrons on membrane systems, while the effect of generation was ambiguous. At higher dendron concentrations, the structure of membranes became disturbed, and membranes were prone to forming bigger aggregates, as visualized by SEM. This might have implications for blood flow disturbances when used in vivo. We propose to introduce blood viscosity measurements in early stages of investigation as they can help to optimize drug-like properties of potential drug carriers.

Automated summary

Drug delivery by dendron-based nanoparticles is widely studied for medical purposes. This study investigated the interaction of amphiphilic dendrons with blood samples. The researchers found a concentration-dependent increase in whole blood viscosity, particularly in males, likely caused by the formation of aggregates. The interaction was determined to be electrostatic in nature. Higher dendron concentrations disrupted membrane structures and increased the likelihood of forming larger aggregates, potentially impacting blood flow when used in vivo. Blood viscosity measurements were suggested for early-stage investigations to optimize drug carrier properties.