Biological drug therapy for ocular angiogenesis: Anti‐VEGF agents and novel strategies based on nanotechnology

Abstract

Currently, biological drug therapy for ocular angiogenesis treatment is based on the administration of anti‐VEGF agents via intravitreal route. The molecules approved with this purpose for ocular use include pegaptanib, ranibizumab, and aflibercept, whereas bevacizumab is commonly off‐label used in the clinical practice. The schedule dosage involves repeated intravitreal injections of anti‐VEGF agents to achieve and maintain effective concentrations in retina and choroids, which are administrated as solutions form. In this review article, we describe the features of different anti‐VEGF agents, major challenges for their ocular delivery and the nanoparticles in development as delivery system of them. In this way, several polymeric and lipid nanoparticles are explored to load anti‐VEGF agents with the aim of achieving sustained drug release and thus, minimize the number of intravitreal injections required. The main challenges were focused in the loading the molecules that maintain their bioactivity after their release from nanoparticulate system, followed the evaluation of them through studies of formulation stability, pharmacokinetic, and efficacy in in vitro and in vivo models. The analysis was based on the information published in peer‐reviewed published papers relevant to anti‐VEGF treatments and nanoparticles developed as ocular anti‐VEGF delivery system.

Low-dose melittin is safe for intravitreal administration and ameliorates inflammation in an experimental model of uveitis

“…The concentrations of MEL safe for intravitreal administration also showed in vivo antiangiogenic activity in the CAM assay. This effect was similar to the positive control, bevacizumab, which is an anti-vascular endothelial growth factor (VEFG) monoclonal antibody highly applied in clinical practice to treat ocular neovascularization ( Formica et al., 2021 ). Other studies have explored the antiangiogenic activity of MEL, especially for cancer treatment ( Liu et al., 2016 ; Rady et al., 2017 ).…”

Rapamycin and Resveratrol Modulate the Gliotic and Pro-Angiogenic Response in Müller Glial Cells Under Hypoxia

“…Several signaling pathways can regulate VEGF synthesis or secretion. Therefore, a wide variety of compounds are able to modulate VEGF during pathological angiogenesis ( Formica et al, 2021 ; Szymanska et al, 2021 ).…”

Ten Years of Knowledge of Nano-Carrier Based Drug Delivery Systems in Ophthalmology: Current Evidence, Challenges, and Future Prospective

“…The main challenges for an anti-VEGF agent delivery system based on nanotechnology focus on loading molecules that maintain their biological activity after being released from the nanoparticle system, and studying formulation stability, pharmacokinetics, and efficacy in in vivo and in vitro models. 153 …”