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Lipid Nanoparticles For Brain Targeting III. Long-term Stability And In Vivo Toxicity.

P. Blasi, A. Schoubben, G. Traina, G. Manfroni, Lanfranco Barberini, P. Alberti, C. Cirotto, M. Ricci
Published 2013 · Chemistry, Medicine

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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 (<5%) of chemical degradation of the lipid matrix and the surfactant after 4 years of storage at 4°C. Chorioallantoic membrane assay and rat brain histology showed the absence of acute toxicity corroborating previously published data. 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.
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