Pediatric research · 2025
Intravitreal Bevacizumab nanoparticles ameliorates retinal vasculopathy in an in vivo mouse model of retinopathy of prematurity.
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Raghunathan Suganesh, Amadi Ben, Raja Alfiya, Mezu-Ndubuisi Olachi J
Аннотация
BACKGROUND: Nanoparticles enable sustained drug release. Infants with retinopathy of prematurity (ROP) treated with Bevacizumab, an anti-vascular endothelial growth factor monoclonal antibody, develop systemic toxicity due to repeat dosing from a short half-life. We optimized fabrication of Bevacizumab nanoparticles in a mouse oxygen-induced retinopathy (OIR) model.
METHODS: Bevacizumab nanoparticle fabrication was optimized for polymer type and ratio, solvent, drug loading capacity (DL) %, and encapsulation efficiency (EE) %. Nanoparticles were characterized using Scanning electron microscopy (SEM), Transmission electron microscopy (TEM), and Fourier-transform infrared spectroscopy (FTIR). C57BL6/J mice exposed to OIR received intravitreal Empty (n = 18), Bevacizumab-loaded nanoparticles (n = 18), or Free Bevacizumab (n = 12) at P13 to right eyes. Fluorescein Angiography (FA) was performed at P20. Retinal avascular area, arterial tortuosity, and vein width were quantified.
RESULTS: SEM showed spherical nanospheres. TEM and FTIR confirmed drugs within nanospheres. DL and EE were optimized at 2.3% and 80%. There was sustained drug release of 80% at 72 h. FA showed increased retinal avascular area, reduced retinal artery tortuosity, and retinal vein width in Bevacizumab nanoparticle treated right eyes.
CONCLUSIONS: Intravitreal administration of Bevacizumab-loaded nanoparticles significantly improved retinal vasculopathy in mice with OIR, without repeat dosing. Further toxicity studies are needed before clinical translation.
IMPACT: Retinopathy of Prematurity is treated with anti-vascular endothelial growth factor drugs such as Bevacizumab. Anti-VEGF drugs result in systemic toxicity from repeat dosing due to their short half-life. We, for the first time, show the feasibility and optimization of nanoparticle formulation of bevacizumab in a mouse model of ROP. Intravitreal Bevacizumab nanoparticles may prevent systemic toxicity and improve outcomes in infants with ROP.
METHODS: Bevacizumab nanoparticle fabrication was optimized for polymer type and ratio, solvent, drug loading capacity (DL) %, and encapsulation efficiency (EE) %. Nanoparticles were characterized using Scanning electron microscopy (SEM), Transmission electron microscopy (TEM), and Fourier-transform infrared spectroscopy (FTIR). C57BL6/J mice exposed to OIR received intravitreal Empty (n = 18), Bevacizumab-loaded nanoparticles (n = 18), or Free Bevacizumab (n = 12) at P13 to right eyes. Fluorescein Angiography (FA) was performed at P20. Retinal avascular area, arterial tortuosity, and vein width were quantified.
RESULTS: SEM showed spherical nanospheres. TEM and FTIR confirmed drugs within nanospheres. DL and EE were optimized at 2.3% and 80%. There was sustained drug release of 80% at 72 h. FA showed increased retinal avascular area, reduced retinal artery tortuosity, and retinal vein width in Bevacizumab nanoparticle treated right eyes.
CONCLUSIONS: Intravitreal administration of Bevacizumab-loaded nanoparticles significantly improved retinal vasculopathy in mice with OIR, without repeat dosing. Further toxicity studies are needed before clinical translation.
IMPACT: Retinopathy of Prematurity is treated with anti-vascular endothelial growth factor drugs such as Bevacizumab. Anti-VEGF drugs result in systemic toxicity from repeat dosing due to their short half-life. We, for the first time, show the feasibility and optimization of nanoparticle formulation of bevacizumab in a mouse model of ROP. Intravitreal Bevacizumab nanoparticles may prevent systemic toxicity and improve outcomes in infants with ROP.
Предметные рубрики MeSH
AnimalsBevacizumabRetinopathy of PrematurityMice, Inbred C57BLDisease Models, AnimalIntravitreal InjectionsNanoparticlesAngiogenesis InhibitorsMiceVascular Endothelial Growth Factor AAnimals, NewbornFluorescein AngiographyRetinal VesselsSpectroscopy, Fourier Transform InfraredOxygenMicroscopy, Electron, Scanning