In vitro evaluation of the genotoxicity of poly(anhydride) nanoparticles designed for oral drug delivery

Int J Pharm. 2017 May 15;523(1):418-426. doi: 10.1016/j.ijpharm.2017.03.016. Epub 2017 Mar 9.

Abstract

In the last years, the development of nanomaterials has significantly increased due to the immense variety of potential applications in technological sectors, such as medicine, pharmacy and food safety. Focusing on the nanodevices for oral drug delivery, poly(anhydride) nanoparticles have received extensive attention due to their unique properties, such as their capability to develop intense adhesive interactions within the gut mucosa, their modifiable surface and their biodegradable and easy-to-produce profile. However, current knowledge of the possible adverse health effects as well as, toxicological information, is still exceedingly limited. Thus, we investigated the capacity of two poly(anhydride) nanoparticles, Gantrez® AN 119-NP (GN-NP) and Gantrez® AN 119 covered with mannosamine (GN-MA-NP), and their main bulk material (Gantrez® AN 119-Polymer), to induce DNA damage and thymidine kinase (TK+/-) mutations in L5178Y TK+/- mouse lymphoma cells after 24h of exposure. The results showed that GN-NP, GN-MA-NP and their polymer did not induce DNA strand breaks or oxidative damage at concentrations ranging from 7.4 to 600μg/mL. Besides, the mutagenic potential of these nanoparticles and their polymer revealed no significant or biologically relevant gene mutation induction at concentrations up to 600μg/mL under our experimental settings. Considering the non-genotoxic effects of GN-NP and GN-MA-NP, as well as their exceptional properties, these nanoparticles are promising nanocarriers for oral medical administrations.

Keywords: Comet assay; Genotoxicity; Mannosamine; Mouse lymphoma assay; Mutagenicity; Poly(anhydride) nanoparticles.

MeSH terms

  • Administration, Oral
  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • DNA Damage
  • Drug Carriers / toxicity*
  • Maleates / toxicity*
  • Mice
  • Mutagenicity Tests
  • Mutation
  • Nanoparticles / toxicity*
  • Polyvinyls / toxicity*
  • Thymidine Kinase / genetics

Substances

  • Drug Carriers
  • Maleates
  • Polyvinyls
  • polyvinylmethoxyethylene-maleic anhydride copolymer
  • Thymidine Kinase