Frontiers in Genetics (Jun 2015)
Genotoxic evaluation of polymeric nanoparticles
Abstract
An important strategy for optimizing the therapeutic efficacy of many conventional drugs is the development of polymeric nanoparticles (NPs), as it may expand their activities, reduce their toxicity, increase their bioactivity and improve biodistribution. The main objective of this study was to evaluate the genotoxicity of 8 different poly (anhydride) NPs designed for the oral administration of therapeutic compounds by using the comet assay in combination with the enzyme formamidopypiridine DNA-glycosylase (FPG). Furthermore, the mitogen capacity of the NPs was evaluated by the proliferation assay. All NPs were tested at four concentrations (0, 0.5, 1 and 2 mg/mL) in Caco-2 cells after 3 hours of treatment while selected NPs were also tested after 24 h. The comet assay was performed immediately after the treatment and cell proliferation was assessed by counting the treated cells after their incubation at 37 °C for 48h. Cells treated with 1 µM of the photosensitizer Ro 19-8022 plus 5 min of light, as well as cells treated with 100 µM H2O2 were included as positive controls in all the experiments. All NPs studied did not result in any increase in the frequency of strand breaks or alkali-labile sites in Caco-2 cells but they induced a slight concentration-dependent increase in net FPG sensitive sites (oxidized and/or alkylated bases). Furthermore, treated cells did not show changes in levels of proliferation in comparison with the negative control.
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