The Effect of Silica Nanoparticles on Human Corneal Epithelial Cells

Abstract

Ocular drug delivery is an interesting field in current research. Silica nanoparticles (SiNPs) are promising drug carriers for ophthalmic drug delivery. However, little is known about the toxicity of SiNPs on ocular surface cells such as human corneal epithelial cells (HCECs). In this study, we evaluated the cytotoxicity induced by 50, 100 and 150 nm sizes of SiNPs on cultured HCECs for up to 48 hours. SiNPs were up-taken by HCECs inside cytoplasmic vacuoles. Cellular reactive oxygen species generation was mildly elevated, dose dependently, with SiNPs, but no significant decrease of cellular viability was observed up to concentrations of 100 μg/ml for three different sized SiNPs. Western blot assays revealed that both cellular autophagy and mammalian target of rapamycin (mTOR) pathways were activated with the addition of SiNPs. Our findings suggested that 50, 100 and 150 nm sized SiNPs did not induce significant cytotoxicity in cultured HCECs.

Safety of Nonporous Silica Nanoparticles in Human Corneal Endothelial Cells

“…Previously, our group reported the effect of various sizes of SiNPs on cultured human corneal epithelial cells and keratocytes. We verified the lack of significant cytotoxicity of 50, 100, and 150 nm SiNPs up to a concentration of 100 µg/ml in culture media 10 , 11 .…”

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

“…This is about 7.4 times higher than the estimated normal daily human oral exposure. In addition, we previously reported the an in vitro safety level of 100 μg/ml concentration of SiNPs onto cultured corneal epithelial cells 19 . The concentration tested in the current in vivo experiment (10 mg/ml) is 100 times higher than the verified safe concentration (100 μg/ml) for cell cultures.…”

“…Nonporous SiNPs of 100 nm were prepared using the Stöber synthesis method. A detailed description of the manufacturing process of SiNPs has been reported previously 19 , 20 . To synthesize SiNPs of 100 nm, 3 ml of ammonia (NH 4 OH, 28%, Junsei, Tokyo, Japan) and 50 ml of ethyl alcohol (EtOH, anhydrous, 99.5%, Daejung, Kyeonggi, Korea) were first mixed.…”

“…In another report, SiNPs elicited only minimal biological toxicity in intestinal cells compared to marked toxicity caused by zinc oxide NPs 18 . Previously, our group reported the in vitro safety of SiNPs on cultured human corneal epithelial cells and keratocytes 19 , 20 . In our previous study, various sized SiNPs (50, 100, and 150 nm) did not result in any significant impairment of cellular viability after exposure for 24 h to concentrations up to 100 μg/ml.…”

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“…However, recent technological progresses have scaled up the use of silica with notable applications in biomedical fields, drug delivery system 5 , sensor, and commercial field also 6 . Normally silica exposure has been reported to be associated with plethora of health diseases of heart, lung, liver, kidney and even cancer.…”