Format

Send to

Choose Destination
Toxicol Lett. 2017 Jul 5;276:129-137. doi: 10.1016/j.toxlet.2017.05.017. Epub 2017 May 17.

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

Author information

1
Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Avenida Prof. Gama Pinto, 1649-003, Lisboa, Portugal; REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal; Instituto Nacional de Saúde Doutor Ricardo Jorge, I.P. (INSA), Av. Padre Cruz, 1649-16 Lisboa, Portugal.
2
Instituto Nacional de Saúde Doutor Ricardo Jorge, I.P. (INSA), Av. Padre Cruz, 1649-16 Lisboa, Portugal; Centre for Toxicogenomics and Human Health (ToxOmics), Nova Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Rua Câmara Pestana, 6, 1150-082 Lisboa, Portugal.
3
Instituto Nacional de Saúde Doutor Ricardo Jorge, I.P. (INSA), Av. Padre Cruz, 1649-16 Lisboa, Portugal.
4
Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Avenida Prof. Gama Pinto, 1649-003, Lisboa, Portugal; Instituto Nacional de Saúde Doutor Ricardo Jorge, I.P. (INSA), Av. Padre Cruz, 1649-16 Lisboa, Portugal.
5
Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Avenida Prof. Gama Pinto, 1649-003, Lisboa, Portugal.
6
Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Avenida Prof. Gama Pinto, 1649-003, Lisboa, Portugal. Electronic address: asimao@ff.ulisboa.pt.

Abstract

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.

KEYWORDS:

Genotoxicity; Nanomedicine; Nanoparticles characterization; Nanotoxicology; Polymeric nanocarriers

PMID:
28526447
DOI:
10.1016/j.toxlet.2017.05.017
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center