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

ABSTRACT: 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.

SUBMITTER: Yu T

PROVIDER: S-EPMC3476833 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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

Yu Tian T Hubbard Dallin D Ray Abhijit A Ghandehari Hamidreza H

Journal of controlled release : official journal of the Controlled Release Society 20120606 1

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 aspec ...[more]

PMID: 22684119

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Project description:Despite increasing reports of using silica nanoparticles (SNPs) for controlled drug delivery applications, their long-term toxicity profile following intravenous administration remains unexplored. Herein, we investigated the acute (10-day) and subchronic (60-day and 180-day) toxicity of nonporous SNPs of approximately 50 nm (Stöber SNPs50) and approximately 500 nm in diameter (Stöber SNPs500), and mesoporous SNPs of approximately 500 nm in diameter (MSNPs500) upon single-dose intravenous injection into male and female immune-competent inbred BALB/c mice. The Maximum Tolerated Dose (MTD) of the particles was determined 10 days post-injection. The MTD of SNPs was administered and toxicity evaluated over 60 and 180 days. Results demonstrate that Stöber SNPs50 exhibit systemic toxicity with MTD of 103 ± 11 mg.kg-1 for female and 100 ± 6 mg.kg-1 for male mice, respectively. Toxicity was alleviated by increasing the size of the particles (Stöber SNPs500). MTD values of 303 ± 4 mg.kg-1 for female and 300 ± 13 mg.kg-1 for male were observed for Stöber SNPs500. Mesoporous SNPs500 showed considerable systemic sex-related toxicity, with MTDs ranging from 40 ± 2 mg.kg-1 to 95 ± 2 mg.kg-1 for male and female mice, respectively. Studies of SNPs showed blood toxicity as a function of physiochemical properties such as significant differences in the mean corpuscular hemoglobin (MCHC) and platelet number at day 10 and white blood cell count at day 60. Histological examination also showed size-, porosity- and time-dependent tissue toxicity. Stöber SNPs500 caused major toxic effects such as lung thrombosis, cardiac wall fibrosis and calcifications, brain infarctions with necrotizing inflammatory response, infiltrate, retinal injuries with calcification and focal gliosis, renal parenchymal damage and liver lobular inflammation dependent on the dose and time of exposure. However, tissue toxicity and accumulation of SNPs in liver observed at day 10 was greater than at day 60 and much greater than at day 180. In contrast, a dramatic increase in cytokine levels was observed at day 60. Despite the relatively high doses, SNPs did not cause subchronic toxicity at day 180 after single-dose intravenous injection. However, they showed distinct differences in the 60 day in vivo subchronic toxicity and inflammation profile as a function of surface area and size.

Dataset Information

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

Publications

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

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