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In vitro and in vivo evaluation of degradation, toxicity, biodistribution, and clearance of silica nanoparticles as a function of size, porosity, density, and composition.

ABSTRACT: Silica nanoparticles (SiO2 NPs) have potential utility in controlled release. Despite significant research in this area, there is a gap in the understanding of the correlation between SiO2 NP physicochemical properties on the one hand and their degradation in solutions, in cells, and in vivo on the other. Here, we fabricated SiO2 NPs with variations in size, porosity, density, and composition: 100?nm Stöber, 100 and 500?nm mesoporous, 100?nm disulfide-based mesoporous, and 100?nm disulfide-based hollow mesoporous. Degradation profiles over 28?days were investigated in simulated biological fluids and deionized water. Results show Meso 100, and 500 nanoparticles degraded faster at higher pH values. Results from macrophages indicate Meso 100 nanoparticles showed the highest degradation amount (~3.8%). Cytotoxicity evaluation of the particles in Human Aortal Endothelial Cells (HAECs) shows concentration-dependent toxicity for the particles. Results from CD-1 mice show ~53% of Meso 100 nanoparticles (25?mg?kg-1) degraded and were detected in urine after seven days. It was shown nanoparticle porosity and composition as well as pH and ionic strength of the medium play the predominant roles for degradation of SiO2 NPs. Based on histological evaluations, at the injected doses investigated, the particles did not show toxicity.

SUBMITTER: Hadipour Moghaddam SP

PROVIDER: S-EPMC6874921 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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RETRACTED: In vitro and in vivo evaluation of degradation, toxicity, biodistribution, and clearance of silica nanoparticles as a function of size, porosity, density, and composition.

Hadipour Moghaddam Seyyed Pouya SP Mohammadpour Raziye R Ghandehari Hamidreza H

Journal of controlled release : official journal of the Controlled Release Society 20190826

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the corresponding author. Subsequent to the publication of the article Journal of Controlled Release 311–312 (2019) 1–15, in follow up studies in 2021, the corresponding author's lab members noticed significant discrepancies in reproducibility of some of the results reported in this manuscr ...[more]

PMID: 31465825

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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 vitro and in vivo evaluation of degradation, toxicity, biodistribution, and clearance of silica nanoparticles as a function of size, porosity, density, and composition.

Publications

RETRACTED: In vitro and in vivo evaluation of degradation, toxicity, biodistribution, and clearance of silica nanoparticles as a function of size, porosity, density, and composition.

Similar Datasets

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