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

D. Graça, Henriqueta Louro, J. Santos, K. Dias, A.J. Almeida, L. Gonçalves, M.J. Silva, A. Bettencourt

Research output: Contribution to journalArticle

9 Citations (Scopus)

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. © 2017 Elsevier B.V.
Original languageEnglish
Pages (from-to)129-137
Number of pages9
JournalToxicology Letters
Volume276
DOIs
Publication statusPublished - 5 Jul 2017

Keywords

  • Genotoxicity
  • Nanomedicine
  • Nanoparticles characterization
  • Nanotoxicology
  • Polymeric nanocarriers
  • eudragit
  • nanocarrier
  • poly(methyl methacrylate)
  • reactive oxygen metabolite
  • acrylic acid resin
  • drug carrier
  • eudragit rs
  • nanoparticle
  • animal cell
  • Article
  • cell death
  • cell viability
  • comet assay
  • controlled study
  • cytotoxicity
  • drug delivery system
  • fibroblast
  • genotoxicity
  • hydrophobicity
  • in vitro study
  • internalization
  • L929 cell line
  • micronucleus test
  • mouse
  • nanotoxicology
  • nonhuman
  • oxidative stress
  • priority journal
  • screening
  • animal
  • cell line
  • cell survival
  • chemical phenomena
  • chemically induced
  • comparative study
  • DNA damage
  • dose response
  • drug effects
  • metabolism
  • micronucleus
  • particle size
  • pathology
  • Acrylic Resins
  • Animals
  • Cell Line
  • Cell Survival
  • Comet Assay
  • DNA Damage
  • Dose-Response Relationship, Drug
  • Drug Carriers
  • Fibroblasts
  • Hydrophobic and Hydrophilic Interactions
  • Mice
  • Micronuclei, Chromosome-Defective
  • Micronucleus Tests
  • Nanoparticles
  • Oxidative Stress
  • Particle Size
  • Polymethyl Methacrylate
  • Reactive Oxygen Species

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