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The development of effective drug delivery systems is a crusial task for modern medicine. The main problem is the occurrence of non-specific toxicity leading to undesirable side effects in vivo.This article aims at reviewing resent research on the toxicity of polyamidoamine (PAMAM) dendrimers in vivo. The research results show that the toxicity of PAMAM dendrimers and modified nanoparticles depends both on the characteristics of the particles themselves (size, generation and surface charge) and on the administration parameters. It has been shown that cationic PAMAM dendrimers of small and medium generations are non-toxic in vivo when administered intravenously and intraperitoneally to mice at doses up to 10 mg/kg. In turn, anionic, neutral, and modified PAMAM dendrimers do not exhibit toxicity, regardless of the route of administration. Thus, by varying methods of administration, the dose, and modifying the surface of dendrimers, the decrease in toxicity can be achieved, promising a path towards their successfully aplication as drug carriers.

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.

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