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Solid lipid nanoparticles (SLNs) are an alternative drug delivery system compared to emulsions, liposomes and polymeric nanoparticles. Due to their unique sizes and properties, SLNs offer possibility to develop new therapeutic approaches. The ability to incorporate drugs into nanocarriers offers a new prototype in drug delivery that could be used for drug targeting. However, toxicity of these new formulations has not been investigated thus far. In this study, we carried out an in vivo toxicity study. For that mice were divided into three groups and treated intraperitoneally with triestearin-based SLNs (TN), natural wax-based SLNs (VN) or vehicle for 10 days. After that, necropsies, histopathological and hematological analysis, as well as hepatic and renal functions were performed. Our results indicated that both TN and VN were absorbed post-exposure and induced an inflammatory response in adipose tissue. However, histopathological analysis demonstrated the absence of toxicity in both treated groups. In addition, the body weights were similar among the groups and low toxicity was also indicated by the unchanged serum biochemical parameters. This study provides a preliminary data for toxicological studies of two different SLNs in long-term in vivo exposure. However, further studies should be conducted in order to investigate the inflammatory response in order to establish the safety of these SLNs.