Development of Nanoparticle-Hydrogel Drug Delivery System for Sustained Release of Anti-VEGF Peptide in Ocular Neovascularization Treatment.

Vascular Endothelial Growth Factor (VEGF) is a critical factor in pathological neovascularization, making it the primary target for ocular anti-angiogenic therapies. Anti-VEGF treatments suffer from requiring frequent intraocular injections for effective treatment due to limited half-life. This study aimed to utilize a composite nanoparticle-hydrogel drug delivery system consisting of poly(glycerol sebacate) (PGS) nanoparticles and cross-linked hyaluronic acid hydrogel to achieve an extended release of anti-VEGF agent, HRH peptide, with the objective of reducing the frequency of intravitreal injections required for treatment of neovascular diseases. Our findings reveal a promising 42.54% ± 5.99% drug release from HA-PGS NP@HRH within the first 3 months, indicating potential for sustained drug release applications. Cell viability studies demonstrate biocompatibility with human retinal pigment epithelium (ARPE-19) cells and reveal anti-angiogenic effects by binding to VEGF receptors on human umbilical vein endothelial (HUVEC) cells, inhibiting VEGF activity, cell growth (with 55.19% cell viability), and tube formation of HUVECs. In vivo experiments with an oxygen-induced retinopathy (OIR) model demonstrated a suppression of neovascularization in mice treated with PGS NPs@HRH. Our research strives to contribute to the development of these new-generation materials, promising improved treatment efficacy and ultimately enhancing the quality of life for patients affected by these challenging conditions.