Anterior Eye Segment Drug Delivery Systems: Current Treatments and Future Challenges

Molokhia, Sarah; Thomas, Samuel; Garff, Kevin; Mandell, Kenneth J.; Wirostko, Barbara

doi:10.1089/jop.2012.0241

Cited by 85 publications

(65 citation statements)

References 95 publications

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“…Although, all three SiNPs (up to 100 μ g/ml concentration) induced a slight increase of intracellular ROS, the cellular viability and intracellular survival machineries such as mTOR pathway and autophagy remained intact. It is known that ocular drug penetration is difficult and can be hindered by extrinsic and intrinsic ocular barriers such as tear film, mucus barrier, tight junction of the corneal epithelium, hydrophilicity of the corneal epithelium, and hydrophobicity of the corneal stroma 1 . Therefore, efficient ocular drugs should have both hydrophilic and hydrophobic properties and sizes small enough to pass through the above-mentioned barriers for successful intraocular penetration.…”

Section: Discussionmentioning

confidence: 99%

The effect of silica nanoparticles on human corneal epithelial cells

Park

Yim

Park

et al. 2016

Acta Ophthalmologica

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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...

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Section: Discussionmentioning

confidence: 99%

The effect of silica nanoparticles on human corneal epithelial cells

Park

Yim

Park

et al. 2016

Acta Ophthalmologica

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“…However, effective topical drug delivery into the eye is still a challenging issue due to its restrictive barriers known as ocular barriers. These barriers limit the distribution of the drugs in the ocular components and decrease their bioavailability to 1-5% [23]. These barriers are classified into anatomical and physiological barriers [24].…”

Section: Barriers To Topical Ocular Drug Deliverymentioning

confidence: 99%

“…Due to the larger pores and higher pores density, the conjunctival permeability to hydrophilic drugs is [15][16][17][18][19][20][21][22][23][24][25] fold that of the cornea [25]. Drugs permeation through the sclera is nearly half that of the conjunctiva [3].…”

Section: Barriers To Topical Ocular Drug Deliverymentioning

confidence: 99%

Topical Drug Delivery for Effective Treatment of Bacterial Infections of the Anterior Segment of the Eye

El-Bary

Ibrahim

Haza'a

2018

Asian J Pharm Clin Res

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Anterior parts of the eye are susceptible to infections caused by different bacterial species. The use of suitable therapeutic measures in case of ocular infections can be sight saving. The appropriate therapy depends on selecting the right antibacterial as well as an efficient drug delivery system. Despite their accessibility, topical delivery of the selected antibiotic into the anterior ocular parts is still a challenging issue due to the complex nature of the eye. Ocular therapy would be significantly improved by modifying the physicochemical properties of the drug and by prolonging its pre-corneal residence time. This review will help pharmaceutical formulators to identify different parts of the eye and the corresponding bacterial infections, ocular barriers to drug delivery, and general consideration when formulating ocular drug delivery systems for the treatment of eye infections.

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“…Transcorneal iontophoresis can deliver dugs to the anterior chamber, whereas transscleral iontophoresis may deliver drugs to the posterior segment. The efficiency of iontophoresis usually depends on the charge of the drug, electrode placement, and duration of pulse (Molokhia et al 2008(Molokhia et al , 2013.…”

Section: Transcorneal Iontophoresismentioning

confidence: 99%