Abstract::
In this review nanoscale based drug delivery systems particularly in relevance to the antiglaucoma drugs have
been discussed. In addition to that, the latest computational/in silico advances in this field are examined in brief. Using
nanoscale materials for drug delivery, is an ideal option to target tumours and drug can be released at areas of the body
where traditional drugs may fail to act. Nanoparticles, polymeric nanomaterials, single-wall carbon nanotubes (SWCNTs),
quantum dots (QDs), liposomes and gra… Show more
“…In addition to the corneal tear film, there are other obstacles within the eye that limit drug delivery, such as the blood aqueous barrier (BAB) [ 22 ]. The small size and novel properties of ENMs provide a promising platform for bypassing these barriers and targeting drugs for difficult to treat tissues and diseases, such as dry eye [ 53 , 54 ], age-related macular degeneration [ 55 , 56 ], glaucoma [ 57 ], and others [ 58 , 59 ]. However, the toxicity of these formulations remains under studied [ 60 ].…”
Section: The Eye Is a Formidable Barriermentioning
The ocular surface, comprised of the transparent cornea, conjunctiva, and protective tear film, forms a protective barrier defending deeper structures of the eye from particulate matter and mechanical trauma. This barrier is routinely exposed to a multitude of naturally occurring and engineered nanomaterials (ENM). Metallic ENMs are particularly ubiquitous in commercial products with a high risk of ocular exposure, such as cosmetics and sunscreens. Additionally, there are several therapeutic uses for metallic ENMs owing to their attractive magnetic, antimicrobial, and functionalization properties. The increasing commercial and therapeutic applications of metallic ENMs come with a high risk of ocular exposure with poorly understood consequences to the health of the eye. While the toxicity of metallic ENMs exposure has been rigorously studied in other tissues and organs, further studies are necessary to understand the potential for adverse effects and inform product usage for individuals whose ocular health may be compromised by injury, disease, or surgical intervention. This review provides an update of current literature on the ocular toxicity of metallic ENMs in vitro and in vivo, as well as the risks and benefits of therapeutic applications of metallic ENMs in ophthalmology.
“…In addition to the corneal tear film, there are other obstacles within the eye that limit drug delivery, such as the blood aqueous barrier (BAB) [ 22 ]. The small size and novel properties of ENMs provide a promising platform for bypassing these barriers and targeting drugs for difficult to treat tissues and diseases, such as dry eye [ 53 , 54 ], age-related macular degeneration [ 55 , 56 ], glaucoma [ 57 ], and others [ 58 , 59 ]. However, the toxicity of these formulations remains under studied [ 60 ].…”
Section: The Eye Is a Formidable Barriermentioning
The ocular surface, comprised of the transparent cornea, conjunctiva, and protective tear film, forms a protective barrier defending deeper structures of the eye from particulate matter and mechanical trauma. This barrier is routinely exposed to a multitude of naturally occurring and engineered nanomaterials (ENM). Metallic ENMs are particularly ubiquitous in commercial products with a high risk of ocular exposure, such as cosmetics and sunscreens. Additionally, there are several therapeutic uses for metallic ENMs owing to their attractive magnetic, antimicrobial, and functionalization properties. The increasing commercial and therapeutic applications of metallic ENMs come with a high risk of ocular exposure with poorly understood consequences to the health of the eye. While the toxicity of metallic ENMs exposure has been rigorously studied in other tissues and organs, further studies are necessary to understand the potential for adverse effects and inform product usage for individuals whose ocular health may be compromised by injury, disease, or surgical intervention. This review provides an update of current literature on the ocular toxicity of metallic ENMs in vitro and in vivo, as well as the risks and benefits of therapeutic applications of metallic ENMs in ophthalmology.
“… 5 Once entering the eyes, nano-sized particles may subsequently induce toxicity on various ocular cells (eg, cornea, conjunctiva, lens, retina) and ultimately lead to the development of ocular diseases. 5–7 CNTs may also be accumulated in eyes as scaffolds, 8 electrodes of retinal implants, 9 drug delivery 10 and antibacterial agents 11 , 12 during the treatment of ocular diseases. Furthermore, CNTs may be orally or intravenously injected, lung-inhaled, and skin-absorbed followed by circulating in the bloodstream and then translocating to various organs (including eye in addition to frequently studied liver, kidneys, brain, et al).…”
Background
The wide application of multi-walled carbon nanotubes (MWCNTs) in various fields has raised enormous concerns regarding their safety for humans. However, studies on the toxicity of MWCNTs to the eye are rare and potential molecular mechanisms are completely lacking. This study was to evaluate the adverse effects and toxic mechanisms of MWCNTs on human ocular cells.
Methods
Human retinal pigment epithelial cells (ARPE-19) were treated with pristine MWCNTs (7–11 nm) (0, 25, 50, 100 or 200 μg/mL) for 24 hours. MWCNTs uptake into ARPE-19 cells was examined using transmission electron microscopy (TEM). The cytotoxicity was evaluated by CCK-8 assay. The death cells were detected by Annexin V-FITC/PI assay. RNA profiles in MWCNT-exposed and non-exposed cells (n = 3) were analyzed using RNA-sequencing. The differentially expressed genes (DEGs) were identified through the DESeq2 method and hub of which were filtered by weighted gene co-expression, protein–protein interaction (PPI) and lncRNA-mRNA co-expression network analyses. The mRNA and protein expression levels of crucial genes were verified using quantitative polymerase chain reaction (qPCR), colorimetric analysis, ELISA and Western blotting. The toxicity and mechanisms of MWCNTs were also validated in human corneal epithelial cells (HCE-T).
Results
TEM analysis indicated the internalization of MWCNTs into ARPE-19 cells to cause cell damage. Compared with untreated ARPE-19 cells, those exposed to MWCNTs exhibited significantly decreased cell viabilities in a dose-dependent manner. The percentages of apoptotic (early, Annexin V positive; late, Annexin V and PI positive) and necrotic (PI positive) cells were significantly increased after exposure to IC50 concentration (100 μg/mL). A total of 703 genes were identified as DEGs; 254 and 56 of them were, respectively, included in darkorange2 and brown1 modules that were significantly associated with MWCNT exposure. Inflammation-related genes (including
CXCL8, MMP1, CASP3, FOS, CXCL2
and
IL11
) were screened as hub genes by calculating the topological characteristics of genes in the PPI network. Two dysregulated long non-coding RNAs (
LUCAT1
and
SCAT8
) were shown to regulate these inflammation-related genes in the co-expression network. The mRNA levels of all eight genes were confirmed to be upregulated, while caspase-3 activity and the release of CXCL8, MMP1, CXCL2, IL11 and FOS proteins were demonstrated to be increased in MWCNT-treated ARPE-19 cells. MWCNTs exposure also can induce cytotoxicity and increase the caspase-3 activity and the expression of LUCAT1, MMP1, CXCL2, and IL11 mRNA and protein in HCE-T cells.
Conclusion
Our study provides promising biomarkers for monitoring MWCNT-induced eye disorders and targets for developing preventive and therapeutic strategies.
“…Anticancer drugs have several major limitations, which include (but are not limited to): non-specificity, wide biological distribution, short half-life and systemic toxicity ( Taghizadeh, 2015 ). Using nanocarriers can help to minimise these drug-related obstacles and improve the therapeutic action of drugs by allowing for delivery and controlled release at specific target sites ( Sharma and Bhatia, 2021 , Wang, 2021 ). Fig.…”
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