The effect of silica nanoparticles on human corneal epithelial cells

Abstract

1Ocular 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 uptaken 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.The cornea is typically the major route of intraocular transport of topically applied drugs 1 . Corneal epithelial cells constitute the outermost mechanical barrier of the ocular surface 2 . These cells are replenished periodically in every 2 weeks by newly differentiated epithelial cells from the limbal area 2,3 . As a most surface layer, corneal epithelial cells are continuously exposed to the outer atmosphere, therefore, they provide the first line of defense against foreign materials invading the ocular surface 2 . This protective role of corneal epithelial cells, on the other hand, sometimes serves as a mechanical barrier for ocular penetration of topically administered medication 1 . To enhance ocular drug penetration, nanoparticle based drug delivery systems have been intensively investigated with promising results [4][5][6] . Amorphous silica nanoparticles (SiNPs) are some of the most promising nanoparticle systems for ocular drug delivery. SiNPs have stable chemical structures, large surface to volume ratios, ease of surface modification and tolerable biodegradability 7 . Due to these physical properties, biomedical applications of SiNPs have been intensively investigated 7,8 . Recent study suggests that small sized (50 nm) silica nanoparticles are readily permeable into de-epithelialized cornea 9 . However, cytotoxicity is the most significant issue with SiNPs. It is known that the cellular toxicity and biological effect of SiNPs are largely dependent on the size and concentration of the SiNPs 10,11 . In addition, different cell types have shown different susceptibility and patterns of SiNPs nanotoxicity 11,12 . Recently, several studies have demonstrated that SiNPs have no direct cytotoxicity on retinal endothelial cells and retinal neuronal tissue 13 . However, the nanotoxicity of SiNPs on corneal epithelial cells is not fully studied yet although these cells are the first encounters when SiNPs are topically administered for ocular therapy.Herein, monodisperse and non-porous SiNPs with diameters of 50, 100 and 150 nm were employed to investigate how particle siz...

Effect of Nitric Oxide onAcanthamoeba castellanii

“…38 In our previous studies, 50-, 100-, and 150-nm SiNPs had no significant cytotoxicity in cultured human corneal cells. 21,22 The in vivo safety of topical application of 100-nm SiNPs was also reported in rats. 39 Our results demonstrated BPEI cytotoxicity to HCEC at high concentration.…”

“…The detailed procedure for transmission electron microscopic (TEM) observations was described previously. 21,22 A. castellanii was treated with three sizes of SiNPs, BPEI-SiNPs, or BPEI-NO-SiNPs for 24 hours and then fixed with 3.7% paraformaldehyde (Sigma-Aldrich Corp., St. Louis, MO, USA) and 2.5% glutaraldehyde (Sigma-Aldrich Corp.) in 0.1 M phosphate buffer (PB; pH 7.6) overnight. After washing with 0.1 M PB, A. castellanii was fixed with 1% osmium tetroxide (OsO 4 ) in the same buffer for 1 hour.…”

Particle Size Distribution of Bimodal Silica Nanoparticles: A Comparison of Different Measurement Techniques

“…A bimodal SNP sample with an average particle size in the 50 nm to 100 nm range was prepared according to the Stöber method [ 11 , 36 , 37 , 38 ]. 10 mL ethanol with 600 µL ammonium hydroxide solution (25 v / v %) was first mixed for 10 min in a 20 mL scintillation vial (WHEATON ® , VWR International, Budapest, Hungary) and then 300 µL TEOS solution was added quickly while stirring the solution at 500 rpm.…”

Recent achievements in nano-based technologies for ocular disease diagnosis and treatment, review and update

“…Park et al performed a study to assess the cytotoxicity of various sizes of silica NPs (SiNPs) on the surface of ocular cells such as human corneal epithelial cells (HCECs). The findings of this study proposed that cellular autophagy pathway activated with the adding SiNPs without any considerable cytotoxicity in the cultured HCECs [ 107 ].…”