title: In vitro evaluation of the genotoxicity of poly(anhydride) nanoparticles designed for oral drug delivery.
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.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy and Nutrition, University of Navarra, Pamplona, Spain.
authors.forename: T
authors.initials: T
authors.lastname: Iglesias
authors.affiliation: Health Effects Laboratory, Department of Environmental Chemistry, Norwegian Institute for Air Research, Kjeller, Norway.
authors.forename: M
authors.initials: M
authors.lastname: Dusinska
authors.affiliation: Health Effects Laboratory, Department of Environmental Chemistry, Norwegian Institute for Air Research, Kjeller, Norway.
authors.forename: N
authors.initials: N
authors.lastname: El Yamani
authors.affiliation: Pharmacy and Pharmaceutical Technology Department, Faculty of Pharmacy and Nutrition, University of Navarra, Irunlarrea 1, 31008, Pamplona, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Irache
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy and Nutrition, University of Navarra, Pamplona, Spain; IdiSNA, Navarra Institute for Health Research, Spain. Electronic address: amazqueta@unav.es.
authors.forename: A
authors.initials: A
authors.lastname: Azqueta
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy and Nutrition, University of Navarra, Pamplona, Spain; IdiSNA, Navarra Institute for Health Research, Spain.
authors.forename: A
authors.initials: A
authors.lastname: López de Cerain
mesh_terms: D000284:Administration, Oral; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004249:DNA Damage; D004337:Drug Carriers / Q000633:toxicity*; D008298:Maleates / Q000633:toxicity*; D051379:Mice; D009152:Mutagenicity Tests; D009154:Mutation; D053758:Nanoparticles / Q000633:toxicity*; D011145:Polyvinyls / Q000633:toxicity*; D013937:Thymidine Kinase / Q000235:genetics
chemical_list: D004337:Drug Carriers; D008298:Maleates; D011145:Polyvinyls; C058026:polyvinylmethoxyethylene-maleic anhydride copolymer; D013937:Thymidine Kinase
keywords: Comet assay; Genotoxicity; Mannosamine; Mouse lymphoma assay; Mutagenicity; Poly(anhydride) nanoparticles