Effect of thermoresponsive quercetin-nanoemulgel eye drop on VEGF-A–induced corneal neovascularization: In vitro and in vivo investigations

Abstract

Corneal neovascularization (CNV) is a sight-threatening condition with the growth of blood vessels into cornea, which is generally induced by VEGF-A. Recently, the potential of quercetin against VEGF-A activities in the eye has been reported. Unfortunately, its lipophilicity usually causes poor oral bioavailability and insufficient concentrations in the eye tissues. We thus developed formulations of thermoresponsive quercetin nanoemulgel (TQNG) that contained an oil in water quercetin nanoemulsion and a poloxamers-based gel for local treatment of the posterior eye segment neovascularization. Although its in vitro activities against VEGF-A had already been reported, there is a lack of in vivo evidence to support the ability of TQNG to be applied for the treatment of ocular neovascularization. Furthermore, in order to expand its applications for the anterior eye segment neovascularization, TQNG was prepared as an eye drop (TQNG-ED) and investigated its activities against CNV. This study thus aimed to investigate activities of TQNG-ED on VEGF-A–induced CNV in vitro and in vivo . TQNG-ED was prepared and sterilized before determining its anti-neovascularization activities in HUVECs and alkali-induced CNV in rats. The results indicated that TQNG-ED was safe to the corneal cell line and the rabbits' eye according to the short time exposure test and the modified Draize test, respectively. It exhibited promising inhibitory activities on VEGF-A–induced tube formation in HUVECs and CNV in alkali-burned rats' cornea via inhibition of VEGF-A activities and downregulation of VEGF-A receptors. Consequently, TQNG-ED could be accepted as a potential topical therapy of CNV for further clinical studies.