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Updated: Mar 17, 2026
Retinal Pathophysiological Evaluation in a Rat Model
Published on: May 6, 2022
Therapeutic effect of apatinib-loaded nanoparticles on diabetes-induced retinal vascular leakage
Ji Hoon Jeong1, Hong Khanh Nguyen2, Jung Eun Lee1
1School of Pharmacy, Sungkyunkwan University, Suwon.
Abstract:
Apatinib, a novel and selective inhibitor of vascular endothelial growth factor (VEGF) receptor 2, has been demonstrated recently to exhibit anticancer efficacy by inhibiting the VEGF signaling pathway. Given the importance of VEGF in retinal vascular leakage, the present study was designed to investigate whether apatinib-loaded polymeric nanoparticles inhibit VEGF-mediated retinal vascular hyperpermeability and block diabetes-induced retinal vascular leakage. For the delivery of water-insoluble apatinib, the drug was encapsulated in nanoparticles composed of human serum albumin (HSA)-conjugated polyethylene glycol (PEG). In vitro paracellular permeability and transendothelial electric resistance assays showed that apatinib-loaded HSA-PEG (Apa-HSA-PEG) nanoparticles significantly inhibited VEGF-induced endothelial hyperpermeability in human retinal microvascular endothelial cells. In addition, they substantially reduced the VEGF-induced junctional loss and internalization of vascular endothelial-cadherin, a major component of endothelial junction complexes. In vivo intravitreal injection of Apa-HSA-PEG nanoparticles in mice blocked VEGF-induced retinal vascular leakage. These in vitro and in vivo data indicated that Apa-HSA-PEG nanoparticles efficiently blocked VEGF-induced breakdown of the blood-retinal barrier. In vivo experiments with streptozotocin-induced diabetic mice showed that an intravitreal injection of Apa-HSA-PEG nanoparticles substantially inhibited diabetes-induced retinal vascular leakage. These results demonstrated, for the first time, that apatinib-loaded nanoparticles may be a promising therapeutic agent for the prevention and treatment of diabetes-induced retinal vascular disorders.
Insights
Apatinib-loaded nanoparticles effectively block vascular endothelial growth factor (VEGF)-induced retinal vascular leakage and diabetes-induced damage. This novel nanoparticle formulation shows promise for treating retinal vascular disorders.
Area of Science:
- Ophthalmology
- Nanomedicine
- Pharmacology
Background:
- Vascular Endothelial Growth Factor (VEGF) plays a critical role in retinal vascular leakage.
- Diabetes can induce significant retinal vascular damage and leakage.
- Apatinib, a VEGF receptor 2 inhibitor, has shown anticancer effects.
Purpose of the Study:
- To investigate if apatinib-loaded polymeric nanoparticles can inhibit VEGF-mediated retinal vascular hyperpermeability.
- To determine the efficacy of these nanoparticles in blocking diabetes-induced retinal vascular leakage.
- To evaluate the potential of apatinib nanoparticles as a therapeutic agent for diabetic retinopathy.
Main Methods:
- Apatinib was encapsulated in human serum albumin (HSA)-conjugated polyethylene glycol (PEG) nanoparticles (Apa-HSA-PEG).
- In vitro assays assessed the effect of Apa-HSA-PEG on VEGF-induced endothelial hyperpermeability in human retinal microvascular endothelial cells.
- In vivo studies involved intravitreal injections in mice to evaluate the blockade of VEGF-induced and diabetes-induced retinal vascular leakage.
Main Results:
- Apa-HSA-PEG nanoparticles significantly inhibited VEGF-induced endothelial hyperpermeability in vitro.
- These nanoparticles reduced VEGF-induced loss of vascular endothelial-cadherin and junctional complexes.
- Intravitreal Apa-HSA-PEG administration blocked both VEGF-induced and diabetes-induced retinal vascular leakage in vivo.
- The nanoparticles effectively prevented the breakdown of the blood-retinal barrier.
Conclusions:
- Apatinib-loaded HSA-PEG nanoparticles efficiently inhibit VEGF-mediated retinal vascular leakage.
- These nanoparticles demonstrate significant potential in preventing and treating diabetes-induced retinal vascular disorders.
- Apa-HSA-PEG nanoparticles represent a promising therapeutic strategy for managing diabetic retinopathy.
