Ocular delivery of sunitinib-loaded nanoparticles doped in tragacanthic acid hydrogel in treatment of diabetic retinopathy in rats

Abstract

OBJECTIVE: Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus. This study aimed to compare the effect of sunitinib-loaded poly (glycerol sebacate) (PGS)/gelatin nanoparticles doped in an injectable hydrogel with bevacizumab as a standard treatment of DR. METHODS: The shear-sensitive hydrogel was prepared based on tragacanthic acid (TA) cross-linked with sodium acetate. DR was induced in rats by streptozotocin (STZ), and the animals were injected intravitreally a single dose of 20 microL sunitinib solution in three different concentrations (12.5, 25, and 50 microg/mL), sunitinib-loaded nanoparticles in hydrogel (413 microg/mL) and bevacizumab solution (6.25 mg/mL). The efficacy of the treatments was studied by histological and immunohisitological tests, angiogenesis, and optical coherence tomography (OCT). Vascular endothelial growth factor (VEGF) concentration was measured in the retina. RESULTS: The results revealed that 20 microL of sunitinib with the concentration of 25 microg/mL was effective in DR without any disruption in the retina or any other side effects. This dose was considered the therapeutic dose for nanoparticles. Sunitinib loaded PGS/gelatin nanoparticles that were incorporated in the injectable hydrogel were as effective as bevacizumab in controlling DR. Although sunitinib solution reduced VEGF production and neovascularization in the retina compared to the negative control group, it was not as suitable as the nanoparticles. TA-based hydrogel showed no toxicity on the normal retina, and the angiography and histologic studies confirmed the VEGF results.' CONCLUSIONS: Sunitinib nanoparticles doped in TA hydrogel may be an appropriate substitution of bevacizumab in the treatment of DR.