In vivo biodistribution and pharmacokinetics of silica nanoparticles as a function of geometry, porosity and surface characteristics

The in vivo biodistribution and pharmacokinetics of silica nanoparticles (SiO2) with systematically varied geometries, porosities, and surface characteristics were investigated in immune-competent CD-1 mice via the intravenous injection. The nanoparticles were taken up extensively by the liver and spleen. Mesoporous SiO2 exhibited higher accumulation in the lung than nonporous SiO2 of similar size. This accumulation was reduced by primary amine modification of the nanoparticles. High aspect ratio, amine-modified mesoporous nanorods showed enhanced lung accumulation compared to amine-modified mesoporous nanospheres. Accumulation of the nanoparticles was mainly caused by passive entrapment in the discontinuous openings in the endothelium of the liver and spleen or in the pulmonary capillaries, and was highly dependent on nanoparticle hydrodynamic size in circulation. The SiO2 were likely internalized by the reticulo-endothelial system (RES) following physical sequestration in the liver and spleen. The nanoparticles that were transiently associated with the lung were re-distributed out of this organ without significant internalization. Pharmacokinetic analysis showed that all SiO2 were rapidly cleared from systemic circulation. Amine-modified or nonporous nanoparticles possessed a higher volume of distribution at steady state than their pristine counterparts or mesoporous SiO2. In all, surface characteristics and porosity played important roles in influencing SiO2 biodistribution and pharmacokinetics. Increasing the aspect ratio of amine-modified mesoporous SiO2 from 1 to 8 resulted in increased accumulation in the lung. (C) 2012 Elsevier B.V. All rights reserved.