Thermo-responsive hydrogel as an anti-VEGF drug delivery system to inhibit retinal angiogenesis in Rex rabbits

BACKGROUND: Wet age-related macular degeneration (Wet AMD) has been treated clinically by intravitreal injection of bevacizumab, which is a kind of the anti-VEGF antibody drug. Nevertheless, because of the short half-life and frequent injections, the use of this treatment is limited. OBJECTIVE: To confirm whether mPEG-PLGA-BOX can be considered as a VEGF drug delivery system to inhibit retinal angiogenesis. METHODS: A thermo-responsive hydrogel of methoxy-poly (ethylene glycol)-block-poly (lactic-co-glycolic acid) (mPEG-PLGA-BOX) was synthesized. The thermo-responsive hydrogel mPEG-PLGA-BOX was able to have sol-gel phase transition upon stimulation by the body temperature with improved biocompatibility and biodegradation. The bevacizumab released from mPEG-PLGA-BOX inhibited RF/6A cells according to a JC-1 assay, which indicated that the released bevacizumab was active to be able to suppress the growth of new blood vessels. In an animal study, retinal laser photocoagulation was performed to induce angiogenesis in the eyes of Rex rabbits using an 810-mm laser. RESULTS: The retina was penetrated when the laser power was more than 500 mW and the exposure time was more than 500 ms. New blood vessels were created at the 28th day after retinal laser photocoagulation. At this time, intravitreal 0.05-mL injections of mPEG-PLGA-BOX (bevacizumab) solution were administered. The bevacizumab released from mPEG-PLGA-BOX (bevacizumab) solution suppressed the angiogenesis. In an in vivo study, the histomorphology of the rabbit retina also indicated that mPEG-PLGA-BOX after intravitreal injection is not toxic to the rabbit retina. CONCLUSIONS: Bevacizumab released from mPEG-PLGA-BOX (bevacizumab) solution suppressed angiogenesis, and mPEG-PLGA-BOX can be considered as a novel thermo-responsive hydrogel with potential as a gelling carrier for extended bevacizumab drug release to treat intraocular neovascular diseases.