The role of polymer type and surfactant composition on the toxicological profile of nanoparticles: an <i>in vitro</i> comparative study

Nanotechnology is expanding rapidly, leading to the continual development of new applications. Therefore, it is crucial to understand the effects of nanoparticles (NPs) and their components to develop more efficient formulations with greater potential applications. Here, we evaluated the influence of polymer and surfactant composition on NP toxicity. Our results revealed significant variations in toxicity based on NP composition. The type of polymer used to prepare the NPs affects their properties, especially in terms of cell tolerance. Notably, cell viability ranged from 6% to 100% depending on the NPs' composition. In general, NPs based on Eudragit^® RL 100 exhibited greater cytotoxicity and hemolysis rates than those based on PCL, PLGA, and chitosan. This highlights the critical role of polymer selection in determining toxicity. Additionally, including Span 80^® in the NP matrix amplified its toxic effects, which emphasizes the importance of surfactant choice in NP design. Both nanospheres and nanocapsules based on the same polymer displayed comparable toxicological profiles. Although smaller NPs exhibited higher toxicity, a direct correlation between size and toxicity could not be established, since the increased toxicity of smaller NPs was primarily attributed to the presence of Span 80^® in the composition. Finally, all formulations, except the nanospheres based on Eudragit^® RL 100, maintained colloidal stability in a protein-rich environment, indicating that no secondary structures were formed. Therefore, our data suggest that NP constituents can critically contribute to its toxicity, highlighting the importance of toxicological and safety studies to better understand the effects of nanoformulations.