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WIREs Nanomed Nanobiotechnol
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Toxicity of nanomaterials to the eye

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Abstract What do nanoparticles offer drug delivery to the eye that traditional formulations do not? The underlying concept of nanomedicine is that the nanomaterials have properties that their constituent components do not have. These unique properties are the benefit, but the cost can be more a complicated toxicology assessment. Ocular delivery of therapeutic nanoparticles has the potential to greatly increase the quality of life through maintaining our vision. The eye is composed of multiple tissue types, i.e., epithelium, muscle, immune cells, neural cells, and blood vessels, to name a few. Ocular diseases affect many of these tissues at once. Introduce novel therapeutic nanoparticles and determining mechanisms of toxicity becomes challenging. This review is a survey of what is known about toxicity in experimental nanoparticles for ocular therapeutics. Specific cases are chosen to illustrate a range of toxic effects of nanoparticles in the eye. There is a unique research opportunity for in‐depth toxicology studies of nanoparticles in the eye. This has been made possible by the rapid development of therapeutic nanoparticles in the last few years. WIREs Nanomed Nanobiotechnol 2010 2 317–333 This article is categorized under: Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials

Percentage of corneal lesion after instillation of increasing concentrations of chitosan hydrochloride (UPC1 110) (white), chitosan glutamate (UPG 210) (hatched), CHITO‐1 (dots) and CHITO‐2 (black).56 (*Scale established by Kalin P, 1994. Contribution á la validation d'un test de tolerance oculaire sur la souris. Ph.D. Thesis. University of Lausanne, Switzerland).

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(a) F‐ERG a‐ and b‐wave amplitude values in treated and control groups at different time points. (b) Implicit time of a‐ and b‐waves of flash electroretinography in treatment and control groups at different time points.10.

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Representative light microscopic photographs of laser lesions in various groups at 56 days. Tissues were stained with hematoxylin and eosin. (a) In the control group, noted the fibrovascular proliferation (FVP) arising through the disrupted retinal pigment epithelium (RPE) and Bruch's membrane and infiltrating the retina. The scale bar represents 100 um. (b) In the 400 ug DA‐loaded PLGA nanoparticle treatment group,note the prominent defects in the RPE and Bruch's membrane with a striking inhibition of FVP. The retina is drawn into the defect. (c) In the 200 ug DA‐loaded PLGA nanoparticle treatment grouping, note the prominent inhibition of FVP, and is similar to (b). (d) In the 50 ug DA‐loaded PLGA nanoparticle treatment group, we noted the prominent inhibition of FVP, and was similar to (b).10.

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Scanning electron microscopy image of dexamethasone acetate–loaded (D,L‐lactide‐co‐glycolide) nanoparticles (scale bar 1 um).10.

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Gross postmortem evaluations were done on all eyes for signs of toxicity, inflammation, and physical trauma. The x‐axis represents the percentage of all eyes for which the characteristic was noted. Results of gross observations of eyes injected via the intravitreous route. Inflammation refers to apparent inflammation anywhere in the eye, whereas haze and membranous opacity suggest inflammatory infiltrates in vitreous.3.

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Gross photographs of eye cups (a, c) and cryosections (b, d, e) from eyes injected intravitreally with PBS (a, b) or chitosan nanoparticles (c–d). (a) The rabbit retina has blood vessels only in the medullary rays (double arrow) that emanate from the optic nerve head, whereas the rest of the retina is avascular. (b) The retinal blood vessels are on the surface of the retina (arrow) and the nuclei of neurons are in three layers: monolayer of ganglion cells innermost, the inner nuclear layer in the middle, and the outer nuclear layer, which contains the nuclei of the photoreceptors. Chitosan‐induced inflammation was characterized by a large white blood cell infiltrate in the vitreous, which has the appearance of a membranous opacity in the gross photograph (arrow in c). Inflammatory cells were apparent on the surface of the retina in cryosections (asterisk in d). Bars indicate (a, c) 1 mm; (b, d) 20 µm. (b, d) Hematoxylin and eosin (H and E) stained sections.3.

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Effects of exposure of freshly isolated whole mouse serum on the surface charge (diamond) and mean hydrodynamic diameter (circle) of chitosan‐DNA nanoparticles. Error bar indicates the standard deviation of at least three measurements.58.

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Physical characterization of chitosan‐DNA nanoparticles. (a) SEM image of nanoparticles. (b) Effect of N/P ratio on the mean size (diamond) and zeta potential (square) of the nanoparticles. (c) Effect of the pH of the nanoparticle suspension on the zeta potential of the nanoparticles.58.

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Ocular surface structures of chitosan nanoparticle (CSNP)‐treated (OD) and control (OS) rabbit eyes. Rabbits were exposed to CSNPs for 24 h. Representative conjunctival impression cytology (a, b) and conjunctival (c, d), and corneal (e, f) sections are shown. Conjunctival and corneal epithelia from both control and treated eyes displayed normal cell layers and morphology. No signs of tissue edema were observed in any structure studied after exposure to CSNPs compared with controls. Scale bar, 100 um.6.

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