Toxicity screening of a novel poly(methylmethacrylate)-Eudragit nanocarrier on L929 fibroblasts

- An integrated approach was used to compare the in vitro toxicity of two poly(methylmethacrylate)-based nanocarriers.
- Physicochemical characterization was conducted in water as well as in cell media.
- For toxicity assessment several endpoints were analyzed using L929 fibroblast.
- Toxicity screening of PMMA-Eudragit nanoparticles enables its further development towards applications for drug delivery.

Translation of innovative drug delivery nanosystems into the market involves an early toxicity screening in the development phase. Previously, we showed that inclusion of the polymer Eudragit (EUD) into poly(methylmethacrylate) (PMMA) nanoparticles (NP) resulted in a novel nanocarrier (PMMA-EUD) with an improved biomedical performance. The safety of this novel nanoparticulate system (PMMA-EUDNPs) was assessed in this work and compared to that of the original PMMANPs by using an integrated approach, comprising in vitro toxicity assessment and NPs physicochemical characterization in water and cell medium. For toxicity assessment several endpoints were analysed, including cell death, oxidative stress, and genotoxicity using L929 fibroblasts. PMMA-EUDNPs proved to be more hydrophobic than the original PMMANPs. Also, charge of both NPs was strongly affected by cell medium. On the other hand, the novel nanosystem was easily uptaken by L929 cells and did not display relevant in vitro cytotoxic or genotoxic effects. On the contrary, PMMANPs were less internalized in cells and proved to be genotoxic, as measured by the micronucleus assay. To conclude, our results provide initial evidence about the safety of the novel and promising PMMA-EUD nanoparticulate system, enabling its further development towards applications for drug delivery.