Avaliação in vivo da biodistribuição e efeitos tóxicos de nanotubos de carbono de paredes múltiplas em camundongos

Abstract

Nanotechnology has been increasingly used in the field of biomedical applications. Among the most used nanomaterials are the Multi-Walled Carbon Nanotubes (MWCNTs), due to its high and effective carrier capacity. With increasing use there was also increased concern about its effects on the organism. The toxicity study of nanotubes is quite complex, due to the uniqueness of each manufactured nanoparticle, providing discrepant results of toxicity assessments, both in vitro and in vivo. Therefore, the evaluation of the biodistribution and the systemic toxic capacity of each MWCNT became essential. In the present study, we sought to clarify aspects related to the biodistribution of MWCNTs functionalized with carboxyl groupings (COOH) and their systemic toxic effect in vivo. For this, we injected female Balb-c mice with solutions containing different concentrations of nanotubes (10μg, 20μg and 50μg), and evaluated at different times of exposure (12 hours, 24 hours, 48 hours and 21 days) through two administration routes: intraperitoneal and subcutaneous. The animals remained for 24 hours in metabolic cages for urine collection. Monitoring of the respiration of these animals through spirometry was performed, and the serum was collected for biochemical evaluation of AST, ALT, GGT, CK and urea. The organs of the animals were also removed for calculation of organ weight/body weight index. All animals survived the injection of nanotubes and showed no differences in the volume of urine collected. Spirometry indicated an overall acute increase in tidal volume after nanoinjections, which was restored after 21 days of exposure. This increase occurred more rapidly for animals injected intraperitoneally than for the subcutaneous route. No differences were recorded in the biochemical indicators, while the index showed a decrease in spleen size only at the concentration of 10μg after 21 days. Our results show that the synthesis and functionalization performed for these MWCNTs was effective in producing nanoparticles with good systemic compatibility and low long term toxicity, and in future studies could be safely used as biological carriers.