Lipid nanoparticles for brain targeting III. Long-term stability and in vivo toxicity

Abstract Purpose The aim of the work was to assess the long-term stability and the safety of lipid nanoparticles intended for brain drug delivery. Methods Lipid nanoparticles, prepared by high pressure homogenization, were stored at room temperature and 4 °C and monitored for their mean hydrodynamic diameter and Gaussian distribution width over time. Cetylpalmitate and polysorbate ® 80 chemical integrity were investigated by nuclear magnetic resonance on diagnostic signals. Nanoparticle toxicity was assessed in chicken embryos by chorioallantoic membrane assay and in rodents by brain histological evaluation. Results Data showed nanoparticle stability at 4 °C over a period of time of 4 years with only a limited particle size increase while at room temperature destabilization was observed after 9 months. Nuclear magnetic resonance investigation confirmed the absence ( Conclusions Cetylpalmitate nanoparticle long-term physical and chemical stability, together with the in vivo safety, corroborate the existing evidences of the high value of colloidal lipids as parenteral formulations and carriers for brain drug delivery.