Formulation development of thermoresponsive quercetin nanoemulgels and in vitro investigation of their inhibitory activity on vascular endothelial growth factor-A inducing neovascularization from the retinal pigment epithelial cells

Abstract

Quercetin is one of natural flavonoids. It has ability to hinder neovascularization in cancers by reducing activities of the vascular endothelial growth factor-A (VEGF-A). Regarding this particular activity, quercetin thus has a potential for managing the vasoproliferative retinopathies. Unfortunately, its hydrophobicity resulted in poor ocular bioavailability. A suitable intravitreal formulation should be developed to overcome this problem. This study was conducted to optimize formulations of thermoresponsive quercetin nanoemulgels (T-QNE-Gs) for intravitreal injection and to examine their in vitro for their inhibitory activity on VEGF-A inducing neovascularization from the retinal pigment endothelial cells. T-QNE-Gs were prepared by incorporation of gels consisting of various ratios of Pluronic F127 (F127) to Pluronic F68 (F68), with a fixed concentration of hydroxypropyl methylcellulose, into a quercetin nanoemulsion concentrate. The optimum formulation of T-QNE-Gs was 2F127–1F68 containing F127 and F68 at a 2:1 ratio. After sterilization, S–2F127–1F68 was obtained. The S–2F127–1F68 could flow properly at a room temperature (27 ± 1 °C) and became gel at a temperature of the posterior eye segment (35 ± 1 °C). It effectively inhibited migration and tube formation of the human umbilical vein endothelial cells and suppressed the VEGF-A gene expression and VEGF-A protein levels in the arising retinal pigment epithelial cells under a hypoxic condition. Therefore, S–2F127–1F68 had a potential for treatment of the vassoproliferative retinopathies and can be used for further investigation in animal models.