An Evaluation of the in vivo Safety of Nonporous Silica Nanoparticles: Ocular Topical Administration versus Oral Administration - PubMed (original) (raw)

An Evaluation of the in vivo Safety of Nonporous Silica Nanoparticles: Ocular Topical Administration versus Oral Administration

Martha Kim et al. Sci Rep. 2017.

Abstract

Nonporous silica nanoparticles (SiNPs) have potential as promising carriers for ophthalmic drugs. However, the in vivo safety of ocular topical SiNPs remains unclear. This study investigated the in vivo safety of oral and ocular topical applications of 100 nm-sized SiNPs in Sprague-Dawley rats. The rats were divided into the following four groups: low-dose oral administration (total 100 mg/kg of SiNPs mixed with food for one week), high-dose oral administration (total 1000 mg/kg of SiNPs mixed with food for one week), ocular topical administration (10 mg/ml concentration, one drop, applied to the right eyes four times a day for one month), or a negative control (no SiNP treatment). The rats were observed for 12 weeks to investigate any signs of general or ocular toxicity. During the observation period, no differences were observed in the body weights, food and water intakes, behaviors and abnormal symptoms of the four groups. No animal deaths occurred. After 12 weeks, hematologic, blood biochemical parameters and ophthalmic examinations revealed no abnormal findings in any of the animals. The lack of toxicity of the SiNPs was further verified in autopsy findings of brain, liver, lung, spleen, heart, kidneys, intestine, eyeballs, and ovaries or testes.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1

Body weight of the rats following the SiNP applications. There was no statistically significant difference in the body weights of the different groups (Group 1, control; Group 2, oral intake, 100 mg/kg; Group 3, oral intake, 1000 mg/kg; Group 4, topical application, 10 mg/ml) over the 12-week period.

Figure 2

In vivo corneal effects of the SiNP applications. Digital photographs were obtained every week for 12 weeks. Corneal transparency and limbal vessels were normal in all the treated groups (Group 2, oral intake 100 mg/kg; Group 3, oral intake 1000 mg/kg; Group 4, topical application 10 mg/ml) as compared to those of the controls (Group 1).

Figure 3

In vivo imaging of the optic nerve head following the SiNP applications. All the images were obtained 12 weeks after the treatments. There was no evidence of optic nerve damage or vascular changes in any of the treated groups (Group 2, oral intake 100 mg/kg; Group 3, oral intake 1000 mg/kg; Group 4, topical application 10 mg/ml) compared to the controls (Group 1).

Figure 4

Histopathological findings of organs from the rats treated with SiNPs. Kidney, liver, spleen, lung, and eyeball samples were collected 12 weeks after the SiNP applications. Sections were stained with hematoxylin and eosin (×200): No treatment (Group 1, controls); low-dose oral intake (Group 2, 100 mg/kg); high-dose oral intake (Group 3, 1000 mg/kg); topical application (Group 4, 10 mg/ml).

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An Evaluation of the in vivo Safety of Nonporous Silica Nanoparticles: Ocular Topical Administration versus Oral Administration - PubMed (original) (raw)