Safety and toxicity of nanomaterials for ocular drug delivery applications

Jeong

Hong

et al. 2016

Sci Rep

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.

mentioning

confidence: 99%

The Effect of Silica Nanoparticles on Human Corneal Epithelial Cells

Jeong

Hong

et al. 2016

Sci Rep

“…SiO 2 nanoparticles (SiNPs; sizes: 50, 100, 150 nm) were prepared using the Stöber synthesis method following the previous study 54 . Tetraethylorthosilicate (TEOS, Samchun), ethyl alcohol (EtOH, anhydrous, 99.5%, Daejung, Kyeonggi, Korea), and ammonia solution (NH 4 OH, 28%, Junsei, Tokyo, Japan) were used as materials. To synthesize 50 nm of SiNPs, 2 mL of ammonia and 50 mL of EtOH were first mixed and then 1 mL of TEOS was added to the solution.…”

Section: Methodsmentioning

confidence: 99%

“…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.…”

mentioning

confidence: 99%

The effect of silica nanoparticles on human corneal epithelial cells

Yim

et al. 2016

Acta Ophthalmologica

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...

“…They release the drug over a longer period of time, thereby increasing the therapeutic efficacy. During the course of drug release, the nanowafers dissolve and fade away [ 163 ]. Xiaoyong et al demonstrated the efficacy of axitinib-loaded nanowafers in treating corneal neovascularization using a murine ocular-burn model.…”

Section: Nanocarriers For Anterior Segment Drug Deliverymentioning

confidence: 99%

Ocular Drug Delivery Barriers—Role of Nanocarriers in the Treatment of Anterior Segment Ocular Diseases

et al. 2018

Ocular drug delivery is challenging due to the presence of anatomical and physiological barriers. These barriers can affect drug entry into the eye following multiple routes of administration (e.g., topical, systemic, and injectable). Topical administration in the form of eye drops is preferred for treating anterior segment diseases, as it is convenient and provides local delivery of drugs. Major concerns with topical delivery include poor drug absorption and low bioavailability. To improve the bioavailability of topically administered drugs, novel drug delivery systems are being investigated. Nanocarrier delivery systems demonstrate enhanced drug permeation and prolonged drug release. This review provides an overview of ocular barriers to anterior segment delivery, along with ways to overcome these barriers using nanocarrier systems. The disposition of nanocarriers following topical administration, their safety, toxicity and clinical trials involving nanocarrier systems are also discussed.