Abstract
Cornea is the transparent layer in front of the eye that does not contain blood vessels. Among eye diseases, corneal neovascularization (NV) is one of the major causes of vision loss, since it can also lead to blindness. An herbal extraction containing flavonoid, kaempferol (KA), with antiangiogenic effect was chosen as a candidate drug for inhibited vessel formation. The use of nanomedicine has led to higher drug bioavailability and slow release of the drug as an effective therapeutic formulation in ocular drug delivery. In this study, we prepared gelatin nanoparticles (GNP) with kaempferol encapsulation (GNP-KA) for corneal NV treatment by topical delivery, i.e., eye drops. We found that GNP with/without KA loading was in the size of 85−150 nm, and its zeta potential was around 22−26 mV. The KA entrapment rate of GNP-KA was around 90−98%, and the loading rate was about 4.6%. The TEM results clearly indicated the GNP-KA NPs to be round spheres. The in vitro test involved the adoption of human umbilical vein endothelial cells (HUVECs) for coculture with these nanoparticles. From WST-8 assay, and cell migration examinations, it was evident that GNP-KA had the capacity to inhibit the cell viability and function of HUVECs. The results from in vivo tests such as ocular vessels observation, hematoxylin & eosin (H&E) stain, and metalloproteinases (MMP)/vascular endothelial growth factor (VEGF) quantification revealed the mice’s eyes with corneal NV treated by eye drops containing GNP-KA once daily for 7 days had better therapeutic effects with less vessels in-growths in the cornea, compared to the KA solution group by reducing the production of MMP and VEGF in the cornea. Therefore, we expected to achieve a comfortable treatment with a simple method using nanomedicine (GNP-KA) as ophthalmological agent delivered as eye drops.
Highlights
Corneal disease is a significant global health problem, with visual scarring accounting for about 5% of the blindness worldwide which approximates to 4.9 million people making it the second most common cause of blindness after cataract [1,2,3,4]
The results obtained from the third day of the WST-8 cell viability tests for gelatin nanoparticles (GNP)-KA established the significant cytostatic activity of the successfully prepared NPs by displaying the inhibition of human umbilical vein endothelial cells (HUVECs) cell viability compared to the KA group
Cell migration tests exhibited the effective inhibition of cell migration of the HUVECs in GNP-KA compared to the other groups
Summary
Corneal disease is a significant global health problem, with visual scarring accounting for about 5% of the blindness worldwide which approximates to 4.9 million people making it the second most common cause of blindness after cataract [1,2,3,4]. Corneal NV generally implies to a neovascularization of the cornea from the edge to the middle, a result of an imbalance between vascular epithelium growth factor (VEGF) and anti-angiogenic factors like angiostatin and endostatin [2,5]. It involves the upregulation of angiogenic factors such as metalloproteinases (MMP) causing a degradation of the extracellular matrix and the basement membrane leading to the remaining proteolytic enzymes to enter the space between the epithelium and the corneal stroma[6]. The corneal epithelial cells and macrophages produce VEGF and b-Fibroblast growth factor (bFGF) which enter the space between the corneal epithelium and the stroma through MMPs and stimulate angiogenesis in the cornea [2,7]
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