Development and evaluation of different lipid nanoparticles for drug delivery: study of cytotoxicity in vitro and in vivo

E. Winter, C.D. Pizzol, C. Locatelli, I.F. Kretzer, T.B.C. Pasa
Federal University of Santa Catarina, BR

Keywords: lipid nanoparticles, nanotoxicology, solid lipid nanoparticles, nanostructured lipid carriers, lipid emulsion

Summary:

Lipid nanoparticles has received considerable attention in the field of drug delivery and can be characterized in relation of their lipid core as solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and lipid emulsions (LE). Despite the wide use of lipid nanoparticles, the toxicity of these systems has not been sufficiently investigated. Thus, the aim of this study was evaluate the cytotoxicity of three lipid nanoparticle systems through in vitro and in vivo studies. The formulations consisted of 1% of surfactant mixture and lipids: SLN (100% solid lipid), NLC (50% solid lipid and 50% oil) and LE (100% oil). For in vitro studies VERO cells were used and for in vivo studies, mice were treated daily for 14 days with nanoparticles. Our results indicate that the SLN induced a cytotoxicity in vitro with CC50 values of 0.7 and 0.4 mg/ml after 24 and 48h of incubation. All nanoparticles seem to induce a possible inflammatory process or an immuno-stimulation. All nanoparticles induced lipid peroxidation in animals liver but only SLN and NLC induced an oxidative stress evidenced by a decrease of antioxidant responses. In conclusion, our findings suggest that the lipid composition plays an important role in the nanoparticles toxicity.