Neurotoxicity of poly(propylene imine) glycodendrimers

Abstract

Published results of studies on poly(propylene imine) (PPI) dendrimers indicate their potential use in the treatment of brain cancer or neurodegenerative diseases due to their ability to cross the blood–brain barrier. However, depending on dose, neurotoxicity may occur. Here, we discuss the impact of maltotriose modified PPI dendrimers on rat’s nervous system. Wistar rats were treated intravenously for 14 consecutive days with densely (dense-shell; DS) and partly (open-shell; OS) modified PPI dendrimers at doses established as safe in the previous experiment following a single DS or OS administration. The examination included an estimation of the motility and the clinical symptoms of the respiratory, nervous, and cardiovascular systems. Both DS and OS glycodendrimers (GDs) induced adverse effects at the doses tested. Multiple administrations of PPI-OS had a detrimental influence on rats’ survival. These findings suggest that the dendrimers adversely influence the nervous system and their toxic effects accumulate over time. In PPI-DS treated animals, the harmful effects were less severe but still present. However, with each treatment day, the clinical symptoms in both groups were less severe as if the animals developed tolerance to GDs. We hypothesize that the neurotoxicity of tested dendrimers is related to nanoparticles-induced autophagy.

Keywords:

• Poly(propylene imine)
• dendrimers
• neurotoxicity
• autophagy
• in vivo

Acknowledgements

Patents US 9,877,985 and US 10 022 395 protect the intellectual property.

Disclosure statement

All authors have no relevant conflicts of interest to disclose.

Additional information

Funding

The study was supported by the EIT Health Go Global Award funded by the European Institute of Innovation and Technology (EIT). This body of the European Union receives support from the European Union's Horizon 2020 Research and Innovation Program. The study was also partially funded by National Centre for Research and Development in Poland from ‘BRIdge Alfa’ Program.