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 (SiO(2)) 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 SiO(2) exhibited higher accumulation in the lung than nonporous SiO(2) 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 SiO(2) 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 SiO(2) 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 SiO(2). In all, surface characteristics and porosity played important roles in influencing SiO(2) biodistribution and pharmacokinetics. Increasing the aspect ratio of amine-modified mesoporous SiO(2) from 1 to 8 resulted in increased accumulation in the lung.
Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA.
Tian
T
Yu
Dallin
D
Hubbard
Abhijit
A
Ray
Hamidreza
H
Ghandehari
D000818:Animals; D005260:Female; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry* / Q000493:pharmacokinetics*; D013499:Surface Properties; D014018:Tissue Distribution
D012822:Silicon Dioxide