Abstract
Vascular endothelial growth factor (VEGF) expression increased significantly in the pathogenesis of age-related macular degeneration, which induced the formation of pathological blood vessels. Dexamethasone is an exogenous anti-angiogenic drug while bevacizumab is an endogenous anti-angiogenic drug. They both have been widely used in ophthalmology. However, independent administration is not enough to completely block the development of choroidal neovascularization (CNV), and the number of eyes vitreous injections is limited. Reasonable combination of drugs may produce significantly better therapeutic effect than single drug treatment. The cyclic RGD (cRGD) peptide has a particularly high affinity with retinal pigment epithelial cells, where VEGF secretes from. In this study, we prepared nanoparticles of bevacizumab and dexamethasone with cRGD peptide as the target (aBev/cRGD-DPPNs). The particle size of the aBev/cRGD-DPPNs was 213.8 ± 1.5 nm, SEM results showed that the nano-carriers were well dispersed and spherical. The cell uptake study demonstrated the selectivity of the aBev/cRGD-DPPN to ARPE-19 with αVβ3 over expressed. The aBev/cRGD-DPPNs had a better apoptosis induction effect and an obvious inhibitory effect on migration, invasion, and capillary-like structures formation of human umbilical vein epithelial cells. The fluorescein fundus angiography study, immunohistochemistry and histopathological evaluation showed the aBev/cRGD-DPPNs greatly reduced the development of CNV on a rabbit model.
Highlights
According to the World Health Organization, there are about 1.3 billion people suffering from a certain degree of visual impairment and 36 million are blind worldwide [1]
Characterizationofofthe theaBev/cyclic RGD (cRGD)-DPPNs aBev/cRGD-DPPNs was used as the carrier material of nanoparticles, and the PEI was used regulate was used as the carrier material of nanoparticles, andbranched the branched wastoused to the potential nanoparticles, cRGD peptide regarded as the target for target preparing regulate theofpotential of nanoparticles, cRGDwas peptide was regarded as the for cRGD-DPPNs loaded withloaded dexamethasone
We found that all the DPPNs, the aBev/DPPNs, and the aBev/cRGD-DPPNs inhibited migration of human umbilical vein epithelial cells (HUVECs) (Figure 4b), and the aBev/cRGD-DPPNs showed a smaller migration effect than the DPPNs and the aBev/DPPNs (47.68 ± 9.88% vs. 4.73 ± 1.57%, p < 0.01; 10.95 ± 5.62%)
Summary
According to the World Health Organization, there are about 1.3 billion people suffering from a certain degree of visual impairment and 36 million are blind worldwide [1]. Retinal diseases have become the main cause of blindness, among which age-related macular degeneration (AMD) is the leading cause. AMD is mainly divided into dry AMD and wet AMD [2,3]. Dry AMD is known as atrophic AMD, which is clinically manifested as progressive pigment epithelial atrophy. Wet AMD is called neovascular AMD, which is clinically manifested as active neovascularization under pigment epithelial layer. Patients with dry AMD are much more than those with wet AMD, wet AMD has a high risk of blindness in a short period of time and more than 90% of patients with
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